Top

Published in:

01-12-2015 | NON-THEMATIC REVIEW

Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity

Authors: Jin Feng, Chao Huang, Jonathan D. Wren, Dao-Wen Wang, Jizhou Yan, Jiexin Zhang, Yujie Sun, Xiao Han, Xin A. Zhang

Published in: Cancer and Metastasis Reviews | Issue 4/2015

Abstract

Tetraspanin CD82 suppresses the progression and metastasis of a wide range of solid malignant tumors. However, its roles in tumorigenesis and hematopoietic malignancy remain unclear. Ubiquitously expressed CD82 restrains cell migration and cell invasion by modulating both cell-matrix and cell-cell adhesiveness and confining outside-in pro-motility signaling. This restraint at least contributes to, if not determines, the metastasis-suppressive activity and, also likely, the physiological functions of CD82. As a modulator of cell membrane heterogeneity, CD82 alters microdomains, trafficking, and topography of the membrane by changing the membrane molecular landscape. The functional activities of membrane molecules and the cytoskeletal interaction of the cell membrane are subsequently altered, followed by changes in cellular functions. Given its pathological and physiological importance, CD82 is a promising candidate for clinically predicting and blocking tumor progression and metastasis and also an emerging model protein for mechanistically understanding cell membrane organization and heterogeneity.

Chiang, A. C., & Massague, J. (2008). Molecular basis of metastasis. The New England Journal of Medicine, 359(26), 2814–2823. doi:10.1056/NEJMra0805239.PubMedCentralPubMedCrossRef

Valastyan, S., & Weinberg, R. A. (2011). Tumor metastasis: molecular insights and evolving paradigms. Cell, 147(2), 275–292. doi:10.1016/j.cell.2011.09.024.PubMedCentralPubMedCrossRef

Dong, J. T., Lamb, P. W., Rinker-Schaeffer, C. W., Vukanovic, J., Ichikawa, T., Isaacs, J. T., et al. (1995). KAI1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2. Science, 268(5212), 884–886.PubMedCrossRef

Zoller, M. (2009). Tetraspanins: push and pull in suppressing and promoting metastasis. Nature Reviews Cancer, 9(1), 40–55. doi:10.1038/nrc2543.PubMedCrossRef

Liu, W. M., & Zhang, X. A. (2006). KAI1/CD82, a tumor metastasis suppressor. Cancer Letters, 240(2), 183–194. doi:10.1016/j.canlet.2005.08.018.PubMedCrossRef

Tonoli, H., & Barrett, J. C. (2005). CD82 metastasis suppressor gene: a potential target for new therapeutics? Trends in Molecular Medicine, 11(12), 563–570. doi:10.1016/j.molmed.2005.10.002.PubMedCrossRef

Miranti, C. K. (2009). Controlling cell surface dynamics and signaling: how CD82/KAI1 suppresses metastasis. Cellular Signalling, 21(2), 196–211. doi:10.1016/j.cellsig.2008.08.023.PubMedCrossRef

Malik, F. A., Sanders, A. J., & Jiang, W. G. (2009). KAI-1/CD82, the molecule and clinical implication in cancer and cancer metastasis. Histology and Histopathology, 24(4), 519–530.PubMed

Tsai, Y. C., & Weissman, A. M. (2011). Dissecting the diverse functions of the metastasis suppressor CD82/KAI1. FEBS Letters, 585(20), 3166–3173. doi:10.1016/j.febslet.2011.08.031.PubMedCentralPubMedCrossRef

10.

Jackson, P., Marreiros, A., & Russell, P. J. (2005). KAI1 tetraspanin and metastasis suppressor. The International Journal of Biochemistry & Cell Biology, 37(3), 530–534. doi:10.1016/j.biocel.2004.08.009.CrossRef

11.

Lee, J. H., Seo, Y. W., Park, S. R., Kim, Y. J., & Kim, K. K. (2003). Expression of a splice variant of KAI1, a tumor metastasis suppressor gene, influences tumor invasion and progression. Cancer Research, 63(21), 7247–7255.PubMed

12.

Strausberg, R. L., Feingold, E. A., Grouse, L. H., Derge, J. G., Klausner, R. D., Collins, F. S., et al. (2002). Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America, 99(26), 16899–16903. doi:10.1073/pnas.242603899.PubMedCrossRef

13.

Wang, H., Zhang, W., Zhao, J., Zhang, L., Liu, M., Yan, G., et al. (2012). N-Glycosylation pattern of recombinant human CD82 (KAI1), a tumor-associated membrane protein. Journal of Proteomics, 75(4), 1375–1385. doi:10.1016/j.jprot.2011.11.013.PubMedCrossRef

14.

Bari, R., Zhang, Y. H., Zhang, F., Wang, N. X., Stipp, C. S., Zheng, J. J., et al. (2009). Transmembrane interactions are needed for KAI1/CD82-mediated suppression of cancer invasion and metastasis. The American Journal of Pathology, 174(2), 647–660. doi:10.2353/ajpath.2009.080685.PubMedCentralPubMedCrossRef

15.

Nagira, M., Imai, T., Ishikawa, I., Uwabe, K. I., & Yoshie, O. (1994). Mouse homologue of C33 antigen (CD82), a member of the transmembrane 4 superfamily: complementary DNA, genomic structure, and expression. Cellular Immunology, 157(1), 144–157. doi:10.1006/cimm.1994.1212.PubMedCrossRef

16.

Shiwu, W. U., Lan, Y., Wenqing, S., Lei, Z., & Yisheng, T. (2012). Expression and clinical significance of CD82/KAI1 and E-cadherin in non-small cell lung cancer. Archives of Iranian Medicine, 15(11), 707–712.PubMed

17.

Knoener, M., Krech, T., Puls, F., Lehmann, U., Kreipe, H., & Christgen, M. (2012). Limited value of KAI1/CD82 protein expression as a prognostic marker in human gastric cancer. Disease Markers, 32(6), 337–342. doi:10.3233/DMA-2012-0896.PubMedCentralPubMedCrossRef

18.

Yang, J. M., Peng, Z. H., Si, S. H., Liu, W. W., Luo, Y. H., & Ye, Z. Y. (2008). KAI1 gene suppresses invasion and metastasis of hepatocellular carcinoma MHCC97-H cells in vitro and in animal models. Liver International, 28(1), 132–139. doi:10.1111/j.1478-3231.2007.01620.x.PubMedCrossRef

19.

Scarpino, S., Duranti, E., Giglio, S., Di Napoli, A., Galafate, D., Del Bufalo, D., et al. (2013). Papillary carcinoma of the thyroid: high expression of COX-2 and low expression of KAI-1/CD82 are associated with increased tumor invasiveness. Thyroid, 23(9), 1127–1137. doi:10.1089/thy.2011.0421.PubMedCrossRef

20.

Zhang, B., Liu, W., Li, L., Lu, J., Liu, M., Sun, Y., et al. (2013). KAI1/CD82 and cyclin D1 as biomarkers of invasion, metastasis and prognosis of laryngeal squamous cell carcinoma. International Journal of Clinical and Experimental Pathology, 6(6), 1060–1067.PubMedCentralPubMed

21.

Xu, J. H., Guo, X. Z., Ren, L. N., Shao, L. C., & Liu, M. P. (2008). KAI1 is a potential target for anti-metastasis in pancreatic cancer cells. World Journal of Gastroenterology, 14(7), 1126–1132.PubMedCentralPubMedCrossRef

22.

Richardson, M. M., Jennings, L. K., & Zhang, X. A. (2011). Tetraspanins and tumor progression. Clinical and Experimental Metastasis, 28(3), 261–270. doi:10.1007/s10585-010-9365-5.PubMedCrossRef

23.

Yang, X., Wei, L. L., Tang, C., Slack, R., Mueller, S., & Lippman, M. E. (2001). Overexpression of KAI1 suppresses in vitro invasiveness and in vivo metastasis in breast cancer cells. Cancer Research, 61(13), 5284–5288.PubMed

24.

Nishioka, C., Ikezoe, T., Furihata, M., Yang, J., Serada, S., Naka, T., et al. (2013). CD34(+)/CD38(-) acute myelogenous leukemia cells aberrantly express CD82 which regulates adhesion and survival of leukemia stem cells. International Journal of Cancer, 132(9), 2006–2019. doi:10.1002/ijc.27904.CrossRef

25.

Burchert, A., Notter, M., Dietrich Menssen, H., Schwartz, S., Knauf, W., Neubauer, A., et al. (1999). CD82 (KAI1), a member of the tetraspan family, is expressed on early haemopoietic progenitor cells and up-regulated in distinct human leukaemias. British Journal of Haematology, 107(3), 494–504.PubMedCrossRef

26.

Termini, C. M., Cotter, M. L., Marjon, K. D., Buranda, T., Lidke, K. A., & Gillette, J. M. (2014). The membrane scaffold CD82 regulates cell adhesion by altering alpha4 integrin stability and molecular density. Molecular Biology of the Cell, 25(10), 1560–1573. doi:10.1091/mbc.E13-11-0660.PubMedCentralPubMedCrossRef

27.

Nishioka, C., Ikezoe, T., Yang, J., Nobumoto, A., Kataoka, S., Tsuda, M., et al. (2014). CD82 regulates STAT5/IL-10 and supports survival of acute myelogenous leukemia cells. International Journal of Cancer, 134(1), 55–64. doi:10.1002/ijc.28348.CrossRef

28.

Geradts, J., Maynard, R., Birrer, M. J., Hendricks, D., Abbondanzo, S. L., Fong, K. M., et al. (1999). Frequent loss of KAI1 expression in squamous and lymphoid neoplasms. An immunohistochemical study of archival tissues. The American Journal of Pathology, 154(6), 1665–1671. doi:10.1016/S0002-9440(10)65422-3.PubMedCentralPubMedCrossRef

29.

Ferrer, M., Yunta, M., & Lazo, P. A. (1998). Pattern of expression of tetraspanin antigen genes in Burkitt lymphoma cell lines. Clinical and Experimental Immunology, 113(3), 346–352.PubMedCentralPubMedCrossRef

30.

Wheeler, D. L., Barrett, T., Benson, D. A., Bryant, S. H., Canese, K., Chetvernin, V., et al. (2007). Database resources of the National Center for Biotechnology Information. Nucleic Acids Research, 35(Database issue), D5–D12. doi:10.1093/nar/gkl1031.PubMedCentralPubMedCrossRef

31.

Cheadle, C., Vawter, M. P., Freed, W. J., & Becker, K. G. (2003). Analysis of microarray data using Z score transformation. The Journal of Molecular Diagnostics, 5(2), 73–81. doi:10.1016/S1525-1578(10)60455-2.PubMedCentralPubMedCrossRef

32.

Drucker, L., Tohami, T., Tartakover-Matalon, S., Zismanov, V., Shapiro, H., Radnay, J., et al. (2006). Promoter hypermethylation of tetraspanin members contributes to their silencing in myeloma cell lines. Carcinogenesis, 27(2), 197–204. doi:10.1093/carcin/bgi209.PubMedCrossRef

33.

Tohami, T., Drucker, L., Shapiro, H., Radnay, J., & Lishner, M. (2007). Overexpression of tetraspanins affects multiple myeloma cell survival and invasive potential. FASEB Journal, 21(3), 691–699. doi:10.1096/fj.06-6610com.PubMedCrossRef

34.

Zismanov, V., Lishner, M., Tartakover-Matalon, S., Radnay, J., Shapiro, H., & Drucker, L. (2009). Tetraspanin-induced death of myeloma cell lines is autophagic and involves increased UPR signalling. British Journal of Cancer, 101(8), 1402–1409. doi:10.1038/sj.bjc.6605291.PubMedCentralPubMedCrossRef

35.

Lishner, M., Zismanov, V., Tohami, T., Tartakover-Matalon, S., Elis, A., & Drucker, L. (2008). Tetraspanins affect myeloma cell fate via Akt signaling and FoxO activation. Cellular Signalling, 20(12), 2309–2316. doi:10.1016/j.cellsig.2008.08.018.PubMedCrossRef

36.

Zismanov, V., Drucker, L., Attar-Schneider, O., Matalon, S. T., Pasmanik-Chor, M., & Lishner, M. (2012). Tetraspanins stimulate protein synthesis in myeloma cell lines. Journal of Cellular Biochemistry, 113(7), 2500–2510. doi:10.1002/jcb.24126.PubMedCrossRef

37.

Yang, X., Welch, D. R., Phillips, K. K., Weissman, B. E., & Wei, L. L. (1997). KAI1, a putative marker for metastatic potential in human breast cancer. Cancer Letters, 119(2), 149–155.PubMedCrossRef

38.

Yang, X., Wei, L., Tang, C., Slack, R., Montgomery, E., & Lippman, M. (2000). KAI1 protein is down-regulated during the progression of human breast cancer. Clinical Cancer Research, 6(9), 3424–3429.PubMed

39.

Stark, A. M., Tongers, K., Maass, N., Mehdorn, H. M., & Held-Feindt, J. (2005). Reduced metastasis-suppressor gene mRNA-expression in breast cancer brain metastases. Journal of Cancer Research and Clinical Oncology, 131(3), 191–198. doi:10.1007/s00432-004-0629-9.PubMedCrossRef

40.

Malik, F. A., Sanders, A. J., Jones, A. D., Mansel, R. E., & Jiang, W. G. (2009). Transcriptional and translational modulation of KAI1 expression in ductal carcinoma of the breast and the prognostic significance. International Journal of Molecular Medicine, 23(2), 273–278.PubMed

41.

Mooez, S., Malik, F. A., Kayani, M. A., Rashid, R., Zahid, A., & Khan, A. (2011). Expressional alterations and transcript isoforms of metastasis suppressor genes (KAI1 and KiSS1) in breast cancer patients. Asian Pacific Journal of Cancer Prevention, 12(10), 2785–2791.PubMed

42.

Christgen, M., Bruchhardt, H., Ballmaier, M., Krech, T., Langer, F., Kreipe, H., et al. (2008). KAI1/CD82 is a novel target of estrogen receptor-mediated gene repression and downregulated in primary human breast cancer. International Journal of Cancer, 123(10), 2239–2246. doi:10.1002/ijc.23806.CrossRef

43.

Huang, H., Groth, J., Sossey-Alaoui, K., Hawthorn, L., Beall, S., & Geradts, J. (2005). Aberrant expression of novel and previously described cell membrane markers in human breast cancer cell lines and tumors. Clinical Cancer Research, 11(12), 4357–4364. doi:10.1158/1078-0432.CCR-04-2107.PubMedCrossRef

44.

Christgen, M., Christgen, H., Heil, C., Krech, T., Langer, F., Kreipe, H., et al. (2009). Expression of KAI1/CD82 in distant metastases from estrogen receptor-negative breast cancer. Cancer Science, 100(9), 1767–1771. doi:10.1111/j.1349-7006.2009.01231.x.PubMedCrossRef

45.

Huang, C. I., Kohno, N., Ogawa, E., Adachi, M., Taki, T., & Miyake, M. (1998). Correlation of reduction in MRP-1/CD9 and KAI1/CD82 expression with recurrences in breast cancer patients. The American Journal of Pathology, 153(3), 973–983.PubMedCentralPubMedCrossRef

46.

Son, B. H., Choi, J. S., & Lee, J. H. (2005). Prognostic values of KAI1 and survivin expression in an infiltrating ductal carcinoma of the breast. Pathology, 37(2), 131–136.PubMedCrossRef

47.

Malik, F. A., Sanders, A. J., Kayani, M. A., & Jiang, W. G. (2009). Effect of expressional alteration of KAI1 on breast cancer cell growth, adhesion, migration and invasion. Cancer Genomics Proteomics, 6(4), 205–213.PubMed

48.

Bandyopadhyay, S., Zhan, R., Chaudhuri, A., Watabe, M., Pai, S. K., Hirota, S., et al. (2006). Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression. Nature Medicine, 12(8), 933–938. doi:10.1038/nm1444.PubMedCrossRef

49.

Larochelle, A., Gillette, J. M., Desmond, R., Ichwan, B., Cantilena, A., Cerf, A., et al. (2012). Bone marrow homing and engraftment of human hematopoietic stem and progenitor cells is mediated by a polarized membrane domain. Blood, 119(8), 1848–1855. doi:10.1182/blood-2011-08-371583.PubMedCentralPubMedCrossRef

50.

Abe, M., Sugiura, T., Takahashi, M., Ishii, K., Shimoda, M., & Shirasuna, K. (2008). A novel function of CD82/KAI-1 on E-cadherin-mediated homophilic cellular adhesion of cancer cells. Cancer Letters, 266(2), 163–170. doi:10.1016/j.canlet.2008.02.058.PubMedCrossRef

51.

Liu, W. M., Zhang, F., Moshiach, S., Zhou, B., Huang, C., Srinivasan, K., et al. (2012). Tetraspanin CD82 inhibits protrusion and retraction in cell movement by attenuating the plasma membrane-dependent actin organization. PloS One, 7(12), e51797. doi:10.1371/journal.pone.0051797.PubMedCentralPubMedCrossRef

52.

Lee, H. A., Park, I., Byun, H. J., Jeoung, D., Kim, Y. M., & Lee, H. (2011). Metastasis suppressor KAI1/CD82 attenuates the matrix adhesion of human prostate cancer cells by suppressing fibronectin expression and beta1 integrin activation. Cellular Physiology and Biochemistry, 27(5), 575–586. doi:10.1159/000329979.PubMedCrossRef

53.

Jee, B. K., Lee, J. Y., Lim, Y., Lee, K. H., & Jo, Y. H. (2007). Effect of KAI1/CD82 on the beta1 integrin maturation in highly migratory carcinoma cells. Biochemical and Biophysical Research Communications, 359(3), 703–708. doi:10.1016/j.bbrc.2007.05.159.PubMedCrossRef

54.

Ruseva, Z., Geiger, P. X., Hutzler, P., Kotzsch, M., Luber, B., Schmitt, M., et al. (2009). Tumor suppressor KAI1 affects integrin alphavbeta3-mediated ovarian cancer cell adhesion, motility, and proliferation. Experimental Cell Research, 315(10), 1759–1771. doi:10.1016/j.yexcr.2009.01.007.PubMedCrossRef

55.

Wei, Q., Zhang, F., Richardson, M. M., Roy, N. H., Rodgers, W., Liu, Y., et al. (2014). CD82 restrains pathological angiogenesis by altering lipid raft clustering and CD44 trafficking in endothelial cells. Circulation, 130(17), 1493–1504. doi:10.1161/CIRCULATIONAHA.114.011096.PubMedCentralPubMedCrossRef

56.

Guo, X. Z., Xu, J. H., Liu, M. P., Kleeff, J., Ho, C. K., Ren, L. N., et al. (2005). KAI1 inhibits anchorage-dependent and -independent pancreatic cancer cell growth. Oncology Reports, 14(1), 59–63.PubMed

57.

Lu, D., Wang, W. X., Xu, Y. Q., Jiang, Q. Y., & Yang, Y. (2007). Inhibitory effect of KAI1 gene on breast cancer cell growth in vitro. Zhonghua Zhong Liu Za Zhi, 29(8), 580–583.PubMed

58.

Tsai, Y. C., Mendoza, A., Mariano, J. M., Zhou, M., Kostova, Z., Chen, B., et al. (2007). The ubiquitin ligase gp78 promotes sarcoma metastasis by targeting KAI1 for degradation. Nature Medicine, 13(12), 1504–1509. doi:10.1038/nm1686.PubMedCrossRef

59.

Lee, J. H., Bae, J. A., Lee, J. H., Seo, Y. W., Kho, D. H., Sun, E. G., et al. (2010). Glycoprotein 90K, downregulated in advanced colorectal cancer tissues, interacts with CD9/CD82 and suppresses the Wnt/beta-catenin signal via ISGylation of beta-catenin. Gut, 59(7), 907–917. doi:10.1136/gut.2009.194068.PubMedCrossRef

60.

Nishioka, C., Ikezoe, T., Takeuchi, A., Nobumoto, A., Tsuda, M., & Yokoyama, A. (2015). The novel function of CD82 and its impact on BCL2L12 via AKT/STAT5 signal pathway in acute myelogenous leukemia cells. Leukemia. doi:10.1038/leu.2015.219.PubMed

61.

Mine, M., Yamaguchi, K., Sugiura, T., Chigita, S., Yoshihama, N., Yoshihama, R., et al. (2015). miR-203 inhibits Frizzled-2 expression via CD82/KAI1 expression in human lung carcinoma cells. PLoS One, 10(7), e0131350. doi:10.1371/journal.pone.0131350.PubMedCentralPubMedCrossRef

62.

Chigita, S., Sugiura, T., Abe, M., Kobayashi, Y., Shimoda, M., Onoda, M., et al. (2012). CD82 inhibits canonical Wnt signalling by controlling the cellular distribution of beta-catenin in carcinoma cells. International Journal of Oncology, 41(6), 2021–2028. doi:10.3892/ijo.2012.1671.PubMedCentralPubMed

63.

Chairoungdua, A., Smith, D. L., Pochard, P., Hull, M., & Caplan, M. J. (2010). Exosome release of beta-catenin: a novel mechanism that antagonizes Wnt signaling. The Journal of Cell Biology, 190(6), 1079–1091. doi:10.1083/jcb.201002049.PubMedCentralPubMedCrossRef

64.

Odintsova, E., Voortman, J., Gilbert, E., & Berditchevski, F. (2003). Tetraspanin CD82 regulates compartmentalisation and ligand-induced dimerization of EGFR. Journal of Cell Science, 116(Pt 22), 4557–4566. doi:10.1242/jcs.00793.PubMedCrossRef

65.

Danglot, L., Chaineau, M., Dahan, M., Gendron, M. C., Boggetto, N., Perez, F., et al. (2010). Role of TI-VAMP and CD82 in EGFR cell-surface dynamics and signaling. Journal of Cell Science, 123(Pt 5), 723–735. doi:10.1242/jcs.062497.PubMedCrossRef

66.

Odintsova, E., van Niel, G., Conjeaud, H., Raposo, G., Iwamoto, R., Mekada, E., et al. (2013). Metastasis suppressor tetraspanin CD82/KAI1 regulates ubiquitylation of epidermal growth factor receptor. The Journal of Biological Chemistry, 288(36), 26323–26334. doi:10.1074/jbc.M112.439380.PubMedCentralPubMedCrossRef

67.

Sridhar, S. C., & Miranti, C. K. (2006). Tetraspanin KAI1/CD82 suppresses invasion by inhibiting integrin-dependent crosstalk with c-Met receptor and Src kinases. Oncogene, 25(16), 2367–2378. doi:10.1038/sj.onc.1209269.PubMedCrossRef

68.

Todeschini, A. R., Dos Santos, J. N., Handa, K., & Hakomori, S. I. (2007). Ganglioside GM2-tetraspanin CD82 complex inhibits met and its cross-talk with integrins, providing a basis for control of cell motility through glycosynapse. The Journal of Biological Chemistry, 282(11), 8123–8133. doi:10.1074/jbc.M611407200.PubMedCrossRef

69.

Takahashi, M., Sugiura, T., Abe, M., Ishii, K., & Shirasuna, K. (2007). Regulation of c-Met signaling by the tetraspanin KAI-1/CD82 affects cancer cell migration. International Journal of Cancer, 121(9), 1919–1929. doi:10.1002/ijc.22887.CrossRef

70.

Mu, Z., Wang, H., Zhang, J., Li, Q., Wang, L., & Guo, X. (2008). KAI1/CD82 suppresses hepatocyte growth factor-induced migration of hepatoma cells via upregulation of Sprouty2. Science in China. Series C, Life Sciences, 51(7), 648–654. doi:10.1007/s11427-008-0086-1.PubMedCrossRef

71.

Lee, C. C., Putnam, A. J., Miranti, C. K., Gustafson, M., Wang, L. M., Vande Woude, G. F., et al. (2004). Overexpression of sprouty 2 inhibits HGF/SF-mediated cell growth, invasion, migration, and cytokinesis. Oncogene, 23(30), 5193–5202. doi:10.1038/sj.onc.1207646.PubMedCrossRef

72.

Xu, C., Zhang, Y. H., Thangavel, M., Richardson, M. M., Liu, L., Zhou, B., et al. (2009). CD82 endocytosis and cholesterol-dependent reorganization of tetraspanin webs and lipid rafts. FASEB Journal, 23(10), 3273–3288. doi:10.1096/fj.08-123414.PubMedCentralPubMedCrossRef

73.

Khanna, P., Chung, C. Y., Neves, R. I., Robertson, G. P., & Dong, C. (2014). CD82/KAI expression prevents IL-8-mediated endothelial gap formation in late-stage melanomas. Oncogene, 33(22), 2898–2908. doi:10.1038/onc.2013.249.PubMedCrossRef

74.

Gabellini, C., Trisciuoglio, D., Desideri, M., Candiloro, A., Ragazzoni, Y., Orlandi, A., et al. (2009). Functional activity of CXCL8 receptors, CXCR1 and CXCR2, on human malignant melanoma progression. European Journal of Cancer, 45(14), 2618–2627. doi:10.1016/j.ejca.2009.07.007.PubMedCrossRef

75.

Delaguillaumie, A., Harriague, J., Kohanna, S., Bismuth, G., Rubinstein, E., Seigneuret, M., et al. (2004). Tetraspanin CD82 controls the association of cholesterol-dependent microdomains with the actin cytoskeleton in T lymphocytes: relevance to co-stimulation. Journal of Cell Science, 117(Pt 22), 5269–5282. doi:10.1242/jcs.01380.PubMedCrossRef

76.

Charrin, S., Manie, S., Thiele, C., Billard, M., Gerlier, D., Boucheix, C., et al. (2003). A physical and functional link between cholesterol and tetraspanins. European Journal of Immunology, 33(9), 2479–2489. doi:10.1002/eji.200323884.PubMedCrossRef

77.

Todeschini, A. R., Dos Santos, J. N., Handa, K., & Hakomori, S. I. (2008). Ganglioside GM2/GM3 complex affixed on silica nanospheres strongly inhibits cell motility through CD82/cMet-mediated pathway. Proceedings of the National Academy of Sciences of the United States of America, 105(6), 1925–1930. doi:10.1073/pnas.0709619104.PubMedCentralPubMedCrossRef

78.

Li, Y., Huang, X., Zhang, J., Li, Y., & Ma, K. (2013). Synergistic inhibition of cell migration by tetraspanin CD82 and gangliosides occurs via the EGFR or cMet-activated Pl3K/Akt signalling pathway. The International Journal of Biochemistry & Cell Biology, 45(11), 2349–2358. doi:10.1016/j.biocel.2013.08.002.CrossRef

79.

Zhang, X. A., & Huang, C. (2012). Tetraspanins and cell membrane tubular structures. Cellular and Molecular Life Sciences, 69(17), 2843–2852. doi:10.1007/s00018-012-0954-0.PubMedCrossRef

80.

Bari, R., Guo, Q., Xia, B., Zhang, Y. H., Giesert, E. E., Levy, S., et al. (2011). Tetraspanins regulate the protrusive activities of cell membrane. Biochemical and Biophysical Research Communications, 415(4), 619–626. doi:10.1016/j.bbrc.2011.10.121.PubMedCentralPubMedCrossRef

81.

Bass, R., Werner, F., Odintsova, E., Sugiura, T., Berditchevski, F., & Ellis, V. (2005). Regulation of urokinase receptor proteolytic function by the tetraspanin CD82. The Journal of Biological Chemistry, 280(15), 14811–14818. doi:10.1074/jbc.M414189200.PubMedCrossRef

82.

Jee, B. K., Park, K. M., Surendran, S., Lee, W. K., Han, C. W., Kim, Y. S., et al. (2006). KAI1/CD82 suppresses tumor invasion by MMP9 inactivation via TIMP1 up-regulation in the H1299 human lung carcinoma cell line. Biochemical and Biophysical Research Communications, 342(2), 655–661. doi:10.1016/j.bbrc.2006.01.153.PubMedCrossRef

83.

You, J., Madigan, M. C., Rowe, A., Sajinovic, M., Russell, P. J., & Jackson, P. (2012). An inverse relationship between KAI1 expression, invasive ability, and MMP-2 expression and activity in bladder cancer cell lines. Urologic Oncology, 30(4), 502–508. doi:10.1016/j.urolonc.2010.02.013.PubMedCrossRef

84.

Schroder, H. M., Hoffmann, S. C., Hecker, M., Korff, T., & Ludwig, T. (2013). The tetraspanin network modulates MT1-MMP cell surface trafficking. The International Journal of Biochemistry & Cell Biology, 45(6), 1133–1144. doi:10.1016/j.biocel.2013.02.020.CrossRef

85.

Arduise, C., Abache, T., Li, L., Billard, M., Chabanon, A., Ludwig, A., et al. (2008). Tetraspanins regulate ADAM10-mediated cleavage of TNF-alpha and epidermal growth factor. The Journal of Immunology , 181(10), 7002–7013.PubMedCrossRef

86.

Xu, D., Sharma, C., & Hemler, M. E. (2009). Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid precursor protein. FASEB Journal, 23(11), 3674–3681. doi:10.1096/fj.09-133462.PubMedCentralPubMedCrossRef

87.

Marreiros, A., Dudgeon, K., Dao, V., Grimm, M. O., Czolij, R., Crossley, M., et al. (2005). KAI1 promoter activity is dependent on p53, junB and AP2: evidence for a possible mechanism underlying loss of KAI1 expression in cancer cells. Oncogene, 24(4), 637–649. doi:10.1038/sj.onc.1208216.PubMedCrossRef

88.

Jackson, P., Ow, K., Yardley, G., Delprado, W., Quinn, D. I., Yang, J. L., et al. (2003). Downregulation of KAI1 mRNA in localised prostate cancer and its bony metastases does not correlate with p53 overexpression. Prostate Cancer and Prostatic Diseases, 6(2), 174–181. doi:10.1038/sj.pcan.4500634.PubMedCrossRef

89.

Guo, C., Liu, Q. G., Zhang, L., Song, T., & Yang, X. (2009). Expression and clinical significance of p53, JunB and KAI1/CD82 in human hepatocellular carcinoma. Hepatobiliary & Pancreatic Diseases International, 8(4), 389–396.

90.

Wu, J., Liang, S., Bergholz, J., He, H., Walsh, E. M., Zhang, Y., et al. (2014). DeltaNp63alpha activates CD82 metastasis suppressor to inhibit cancer cell invasion. Cell Death and Disease, 5, e1280. doi:10.1038/cddis.2014.239.PubMedCentralPubMedCrossRef

91.

Kim, B., Boo, K., Lee, J. S., Kim, K. I., Kim, W. H., Cho, H. J., et al. (2010). Identification of the KAI1 metastasis suppressor gene as a hypoxia target gene. Biochemical and Biophysical Research Communications, 393(1), 179–184. doi:10.1016/j.bbrc.2010.01.118.PubMedCrossRef

92.

Nagao, K., & Oka, K. (2011). HIF-2 directly activates CD82 gene expression in endothelial cells. Biochemical and Biophysical Research Communications, 407(1), 260–265. doi:10.1016/j.bbrc.2011.03.017.PubMedCrossRef

93.

Dai, W., Wang, C., Wang, F., Wang, Y., Shen, M., Chen, K., et al. (2014). Anti-miR-197 inhibits migration in HCC cells by targeting KAI 1/CD82. Biochemical and Biophysical Research Communications, 446(2), 541–548. doi:10.1016/j.bbrc.2014.03.006.PubMedCrossRef

94.

Kim, Y. I., Shin, M. K., Lee, J. W., Chung, J. H., & Lee, M. H. (2009). Decreased expression of KAI1/CD82 metastasis suppressor gene is associated with loss of heterozygosity in melanoma cell lines. Oncology Reports, 21(1), 159–164.PubMed

95.

Upheber, S., Karle, A., Miller, J., Schlaugk, S., Gross, E., & Reuning, U. (2015). Alternative splicing of KAI1 abrogates its tumor-suppressive effects on integrin alphavbeta3-mediated ovarian cancer biology. Cellular Signalling, 27(3), 652–662. doi:10.1016/j.cellsig.2014.11.028.PubMedCrossRef

96.

Gellersen, B., Briese, J., Oberndorfer, M., Redlin, K., Samalecos, A., Richter, D. U., et al. (2007). Expression of the metastasis suppressor KAI1 in decidual cells at the human maternal-fetal interface: regulation and functional implications. The American Journal of Pathology, 170(1), 126–139. doi:10.2353/ajpath.2007.060175.PubMedCentralPubMedCrossRef

97.

Gonzalez, M., Neufeld, J., Reimann, K., Wittmann, S., Samalecos, A., Wolf, A., et al. (2011). Expansion of human trophoblastic spheroids is promoted by decidualized endometrial stromal cells and enhanced by heparin-binding epidermal growth factor-like growth factor and interleukin-1 beta. Molecular Human Reproduction, 17(7), 421–433. doi:10.1093/molehr/gar015.PubMedCrossRef

98.

Wei, X., Liu, S., Wang, X., & Yan, Q. (2012). CD82 expression alters with human endometrial cycles and affects the uterine endometrial receptivity in vitro. Experimental Biology and Medicine (Maywood, N.J.), 237(3), 254–262. doi:10.1258/ebm.2011.011309.CrossRef

99.

Meng, Y. H., Shao, J., Li, H., Hou, Y. L., Tang, C. L., Du, M. R., et al. (2012). CsA improves the trophoblasts invasiveness through strengthening the cross-talk of trophoblasts and decidual stromal cells mediated by CXCL12 and CD82 in early pregnancy. International Journal of Clinical and Experimental Pathology, 5(4), 299–307.PubMedCentralPubMed

100.

Li, M. Q., Tang, C. L., Du, M. R., Fan, D. X., Zhao, H. B., Xu, B., et al. (2011). CXCL12 controls over-invasion of trophoblasts via upregulating CD82 expression in DSCs at maternal-fetal interface of human early pregnancy in a paracrine manner. International Journal of Clinical and Experimental Pathology, 4(3), 276–286.PubMedCentralPubMed

101.

Li, M. Q., Hou, X. F., Shao, J., Tang, C. L., & Li, D. J. (2010). The DSCs-expressed CD82 controls the invasiveness of trophoblast cells via integrinbeta1/MAPK/MAPK3/1 signaling pathway in human first-trimester pregnancy. Biology of Reproduction, 82(5), 968–979. doi:10.1095/biolreprod.109.080739.PubMedCrossRef

102.

Li, M. Q., Hou, X. F., Lv, S. J., Meng, Y. H., Wang, X. Q., Tang, C. L., et al. (2011). CD82 gene suppression in endometrial stromal cells leads to increase of the cell invasiveness in the endometriotic milieu. Journal of Molecular Endocrinology, 47(2), 195–208. doi:10.1530/JME-10-0165.PubMedCrossRef

103.

Gellersen, B., Wolf, A., Kruse, M., Schwenke, M., & Bamberger, A. M. (2013). Human endometrial stromal cell-trophoblast interactions: mutual stimulation of chemotactic migration and promigratory roles of cell surface molecules CD82 and CEACAM1. Biology of Reproduction, 88(3), 80. doi:10.1095/biolreprod.112.106724.PubMedCrossRef

104.

Spring, F. A., Griffiths, R. E., Mankelow, T. J., Agnew, C., Parsons, S. F., Chasis, J. A., et al. (2013). Tetraspanins CD81 and CD82 facilitate alpha4beta1-mediated adhesion of human erythroblasts to vascular cell adhesion molecule-1. PloS One, 8(5), e62654. doi:10.1371/journal.pone.0062654.PubMedCentralPubMedCrossRef

105.

Lin, G., Mela, A., Guilfoyle, E. M., & Goldman, J. E. (2009). Neonatal and adult O4(+) oligodendrocyte lineage cells display different growth factor responses and different gene expression patterns. Journal of Neuroscience Research, 87(15), 3390–3402. doi:10.1002/jnr.22065.PubMedCentralPubMedCrossRef

106.

Mela, A., & Goldman, J. E. (2009). The tetraspanin KAI1/CD82 is expressed by late-lineage oligodendrocyte precursors and may function to restrict precursor migration and promote oligodendrocyte differentiation and myelination. The Journal of Neuroscience, 29(36), 11172–11181. doi:10.1523/JNEUROSCI.3075-09.2009.PubMedCentralPubMedCrossRef

107.

Mela, A., & Goldman, J. E. (2013). CD82 blocks cMet activation and overcomes hepatocyte growth factor effects on oligodendrocyte precursor differentiation. The Journal of Neuroscience, 33(18), 7952–7960. doi:10.1523/JNEUROSCI.5836-12.2013.PubMedCrossRef

108.

Risinger, J. I., Custer, M., Feigenbaum, L., Simpson, R. M., Hoover, S. B., Webster, J. D., et al. (2014). Normal viability of Kai1/Cd82 deficient mice. Molecular Carcinogenesis, 53(8), 610–624. doi:10.1002/mc.22009.PubMed

109.

Choi, U. J., Jee, B. K., Lim, Y., & Lee, K. H. (2009). KAI1/CD82 decreases Rac1 expression and cell proliferation through PI3K/Akt/mTOR pathway in H1299 lung carcinoma cells. Cell Biochemistry and Function, 27(1), 40–47. doi:10.1002/cbf.1532.PubMedCrossRef

110.

Guan-Zhen, Y., Ying, C., Can-Rong, N., Guo-Dong, W., Jian-Xin, Q., & Jie-Jun, W. (2007). Reduced protein expression of metastasis-related genes (nm23, KISS1, KAI1 and p53) in lymph node and liver metastases of gastric cancer. International Journal of Experimental Pathology, 88(3), 175–183. doi:10.1111/j.1365-2613.2006.00510.x.PubMedCentralPubMedCrossRef

111.

Chen, Z., Gu, S., Trojanowicz, B., Liu, N., Zhu, G., Dralle, H., et al. (2011). Down-regulation of TM4SF is associated with the metastatic potential of gastric carcinoma TM4SF members in gastric carcinoma. World Journal of Surgical Oncology, 9, 43. doi:10.1186/1477-7819-9-43.PubMedCentralPubMedCrossRef

112.

Ilhan, O., Celik, S. Y., Han, U., & Onal, B. (2009). Use of KAI-1 as a prognostic factor in gastric carcinoma. European Journal of Gastroenterology & Hepatology, 21(12), 1369–1372. doi:10.1097/MEG.0b013e328323aac9.CrossRef

113.

Jiang, W. X., Song, B. G., Tang, R. Y., & Fang, J. P. (2008). Expression of nm23 and KAI1 and their clinical significance in gallbladder adenocarcinoma. Zhonghua Zhong Liu Za Zhi, 30(6), 441–443.PubMed

114.

Liu, X., Guo, X. Z., Zhang, W. W., Lu, Z. Z., Zhang, Q. W., Duan, H. F., et al. (2011). KAI1 inhibits HGF-induced invasion of pancreatic cancer by sphingosine kinase activity. Hepatobiliary & Pancreatic Diseases International, 10(2), 201–208.CrossRef

115.

Rotterud, R., Fossa, S. D., & Nesland, J. M. (2007). Protein networking in bladder cancer: immunoreactivity for FGFR3, EGFR, ERBB2, KAI1, PTEN, and RAS in normal and malignant urothelium. Histology and Histopathology, 22(4), 349–363.PubMed

116.

Ai, X., Zhang, X., Wu, Z., Ma, X., Ju, Z., Wang, B., et al. (2007). Expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder. Journal of Huazhong University of Science and Technology. Medical Sciences, 27(1), 79–82. doi:10.1007/s11596-007-0123-0.CrossRef

117.

Jackson, P., Rowe, A., & Grimm, M. O. (2007). An alternatively spliced KAI1 mRNA is expressed at low levels in human bladder cancers and bladder cancer cell lines and is not associated with invasive behaviour. Oncology Reports, 18(6), 1357–1363.PubMed

118.

Rowe, A., & Jackson, P. (2006). Expression of KITENIN, a KAI1/CD82 binding protein and metastasis enhancer, in bladder cancer cell lines: relationship to KAI1/CD82 levels and invasive behaviour. Oncology Reports, 16(6), 1267–1272.PubMed

119.

Ouyang, Y. W., Pan, X. L., Peng, Z. L., Qu, Y., & Zhang, H. Y. (2008). Expression of metastasis suppressor gene KAI1 in cervical carcinoma and infections of HPV16 E6, E7 and HPV18 E6/E7. Sichuan Da Xue Xue Bao. Yi Xue Ban, 39(3), 410–413.PubMed

120.

Ouyang, Y. W., Pan, X. L., Qu, Y., Peng, Z. L., Wei, D. P., & Wang, X. (2008). Effect of metastasis suppressor gene KAI1 on the proliferation and invasive ability of cervical carcinoma cells. Sichuan Da Xue Xue Bao. Yi Xue Ban, 39(5), 753–756.PubMed

121.

Park, J. J., Jin, Y. B., Lee, Y. J., Lee, J. S., Lee, Y. S., Ko, Y. G., et al. (2012). KAI1 suppresses HIF-1alpha and VEGF expression by blocking CDCP1-enhanced Src activation in prostate cancer. BMC Cancer, 12, 81. doi:10.1186/1471-2407-12-81.PubMedCentralPubMedCrossRef

122.

Liu, W., Iiizumi-Gairani, M., Okuda, H., Kobayashi, A., Watabe, M., Pai, S. K., et al. (2011). KAI1 gene is engaged in NDRG1 gene-mediated metastasis suppression through the ATF3-NFkappaB complex in human prostate cancer. The Journal of Biological Chemistry, 286(21), 18949–18959. doi:10.1074/jbc.M111.232637.PubMedCentralPubMedCrossRef

123.

Tang, Y., Cheng, Y., Martinka, M., Ong, C. J., & Li, G. (2014). Prognostic significance of KAI1/CD82 in human melanoma and its role in cell migration and invasion through the regulation of ING4. Carcinogenesis, 35(1), 86–95. doi:10.1093/carcin/bgt346.PubMedCrossRef

124.

Gentleman, R. C., Carey, V. J., Bates, D. M., Bolstad, B., Dettling, M., Dudoit, S., et al. (2004). Bioconductor: open software development for computational biology and bioinformatics. Genome Biology, 5(10), R80. doi:10.1186/gb-2004-5-10-r80.PubMedCentralPubMedCrossRef

125.

Gautier, L., Cope, L., Bolstad, B. M., & Irizarry, R. A. (2004). affy—analysis of Affymetrix GeneChip data at the probe level. Bioinformatics, 20(3), 307–315. doi:10.1093/bioinformatics/btg405.PubMedCrossRef

Title: Tetraspanin CD82: a suppressor of solid tumors and a modulator of membrane heterogeneity
Authors: Jin Feng
Chao Huang
Jonathan D. Wren
Dao-Wen Wang
Jizhou Yan
Jiexin Zhang
Yujie Sun
Xiao Han
Xin A. Zhang
Publication date: 01-12-2015
Publisher: Springer US
Published in: Cancer and Metastasis Reviews / Issue 4/2015
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-015-9585-x

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2015

Protease-activated receptors (PARs)—biology and role in cancer invasion and metastasis

Breast carcinoma metastasis suppressor gene 1 (BRMS1): update on its role as the suppressor of cancer metastases

Imaging approaches to assess the therapeutic response of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): current perspectives and future trends of an exciting field in development

EPLIN: a fundamental actin regulator in cancer metastasis?

Insights into brain metastasis in patients with ALK+ lung cancer: is the brain truly a sanctuary?

Neutrophils: important contributors to tumor progression and metastasis

Keynote webinar | Spotlight on antibody–drug conjugates in cancer