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Published in: NeuroMolecular Medicine 1/2019

01-03-2019 | Glioma | Original Paper

Hsc70 Interacts with β4GalT5 to Regulate the Growth of Gliomas

Authors: Guan Sun, Ying Cao, Xueliang Dai, Min Li, Jun Guo

Published in: NeuroMolecular Medicine | Issue 1/2019

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Abstract

Heat shock cognate protein 70 (Hsc70) is a key mediator for the maintenance of intracellular proteins and regulates cellular activities. And it is elevated in various tumor tissues including glioma, which is closely related to the malignancy and poor prognosis of the tumors. However, the effects of Hsc70 on gliomas and its regulatory mechanism have not yet been elucidated. In the present study, we found that Hsc70 was overexpressed in glioma tissues and cultured glioma cells. Furthermore, Hsc70 expression exhibited positive correlation with the grades of gliomas. Knockdown of Hsc70 could effectively inhibit cell proliferation and increase cell apoptosis. Furthermore, we identified that β4GalT5 was a critical target for Hsc70-mediated anti-glioma effects. Blocking β4GalT5 activity could effectively reverse the anti-tumor effect of Hsc70. Taken together, these data indicate that Hsc70 regulates β4GalT5 levels, and possibly plays a role in cell proliferation and apoptosis of glioma.
Literature
go back to reference Beaman, G. M., Dennison, S. R., Chatfield, L. K., & Phoenix, D. A. (2014). Reliability of HSP70 (HSPA) expression as a prognostic marker in glioma. Molecular and Cellular Biochemistry, 393(2), 301–307.CrossRefPubMed Beaman, G. M., Dennison, S. R., Chatfield, L. K., & Phoenix, D. A. (2014). Reliability of HSP70 (HSPA) expression as a prognostic marker in glioma. Molecular and Cellular Biochemistry, 393(2), 301–307.CrossRefPubMed
go back to reference Beckmann, R. P., Mizzen, L. E., & Welch, W. J. (1990). Interaction of Hsp 70 with newly synthesized proteins: Implications for protein folding and assembly. Science, 248(4957), 850–854.CrossRefPubMed Beckmann, R. P., Mizzen, L. E., & Welch, W. J. (1990). Interaction of Hsp 70 with newly synthesized proteins: Implications for protein folding and assembly. Science, 248(4957), 850–854.CrossRefPubMed
go back to reference Bukau, B., & Horwich, A. L. (1998). The Hsp70 and Hsp60 chaperone machines. Cell, 92(3), 351–366.CrossRefPubMed Bukau, B., & Horwich, A. L. (1998). The Hsp70 and Hsp60 chaperone machines. Cell, 92(3), 351–366.CrossRefPubMed
go back to reference Chen, X., Jiang, J., Yang, J., Chen, C., Sun, M., Wei, Y., Guang, X., & Gu, J. (2006). Down-regulation of the expression of beta1, 4-galactosyltransferase V promotes integrin beta1 maturation. Biochemical and Biophysical Research Communication, 343(3), 910–916.CrossRef Chen, X., Jiang, J., Yang, J., Chen, C., Sun, M., Wei, Y., Guang, X., & Gu, J. (2006). Down-regulation of the expression of beta1, 4-galactosyltransferase V promotes integrin beta1 maturation. Biochemical and Biophysical Research Communication, 343(3), 910–916.CrossRef
go back to reference Cui, C., Chen, X., Liu, Y., Cao, B., Xing, Y., Liu, C., Yang, F., Li, Y., Yang, T., Hua, L., Tian, M., Wei, Y., Gong, Y., & Jiang, J.β(2017). β1,4-Galactosyltransferase V activates Notch1 signaling in glioma stem-like cells and promotes their transdifferentiation into endothelial cells. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.RA117.000682.CrossRefPubMed Cui, C., Chen, X., Liu, Y., Cao, B., Xing, Y., Liu, C., Yang, F., Li, Y., Yang, T., Hua, L., Tian, M., Wei, Y., Gong, Y., & Jiang, J.β(2017). β1,4-Galactosyltransferase V activates Notch1 signaling in glioma stem-like cells and promotes their transdifferentiation into endothelial cells. Journal of Biological Chemistry. https://​doi.​org/​10.​1074/​jbc.​RA117.​000682.CrossRefPubMed
go back to reference D’Arrigo, P., Russo, M., Rea, A., Tufano, M., Guadagno, E., Del Basso De Caro, M. L., Pacelli, R., Hausch, F., Staibano, S., Ilardi, G., Parisi, S., & Romano, M. F. (2017). A regulatory role for the co-chaperone FKBP51s in PD-L1 expression in glioma. Oncotarget, 8(40):68291–68304.PubMedPubMedCentral D’Arrigo, P., Russo, M., Rea, A., Tufano, M., Guadagno, E., Del Basso De Caro, M. L., Pacelli, R., Hausch, F., Staibano, S., Ilardi, G., Parisi, S., & Romano, M. F. (2017). A regulatory role for the co-chaperone FKBP51s in PD-L1 expression in glioma. Oncotarget, 8(40):68291–68304.PubMedPubMedCentral
go back to reference Ding, Y., Song, N., Liu, C., He, T., Zhuo, W., He, X., Chen, Y., Song, X., Fu, Y., & Luo, Y. (2012). Heat shock cognate 70 regulates the translocation and angiogenic function of nucleolin. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(9), 126–134.CrossRef Ding, Y., Song, N., Liu, C., He, T., Zhuo, W., He, X., Chen, Y., Song, X., Fu, Y., & Luo, Y. (2012). Heat shock cognate 70 regulates the translocation and angiogenic function of nucleolin. Arteriosclerosis, Thrombosis, and Vascular Biology, 32(9), 126–134.CrossRef
go back to reference Ferguson, S. D. (2011). Malignant gliomas: Diagnosis and treatment. Disease-a-Month, 57(10), 558–569.CrossRefPubMed Ferguson, S. D. (2011). Malignant gliomas: Diagnosis and treatment. Disease-a-Month, 57(10), 558–569.CrossRefPubMed
go back to reference Hantschel, M., Pfister, K., Jordan, A., Scholz, R., Andreesen, R., & Schmitz, G. (2000). Hsp70 plasma membrane expression on primary tumor biopsy material and bone marrow of leukemic patients. Cell Stress and Chaperones, 5(5), 438–442.CrossRefPubMed Hantschel, M., Pfister, K., Jordan, A., Scholz, R., Andreesen, R., & Schmitz, G. (2000). Hsp70 plasma membrane expression on primary tumor biopsy material and bone marrow of leukemic patients. Cell Stress and Chaperones, 5(5), 438–442.CrossRefPubMed
go back to reference Hartl, F. U., & Hayer-Hartl, M. (2002). Molecular chaperones in the cytosol: From nascent chain to folded protein. Science, 295(5561), 1852–1858.CrossRefPubMed Hartl, F. U., & Hayer-Hartl, M. (2002). Molecular chaperones in the cytosol: From nascent chain to folded protein. Science, 295(5561), 1852–1858.CrossRefPubMed
go back to reference Isomoto, H., Oka, M., Yano, Y., Kanazawa, Y., Soda, H., Terada, R., Yasutake, T., Nakayama, T., Shikuwa, S., Takeshima, F., Udono, H., Murata, I., Ohtsuka, K., & Kohno, S. (2003). Expression of heat shock protein (Hsp) 70 and Hsp 40 in gastric cancer. Cancer Letters, 198(2), 219–228.CrossRefPubMed Isomoto, H., Oka, M., Yano, Y., Kanazawa, Y., Soda, H., Terada, R., Yasutake, T., Nakayama, T., Shikuwa, S., Takeshima, F., Udono, H., Murata, I., Ohtsuka, K., & Kohno, S. (2003). Expression of heat shock protein (Hsp) 70 and Hsp 40 in gastric cancer. Cancer Letters, 198(2), 219–228.CrossRefPubMed
go back to reference Jiang, J., Chen, X., Shen, J., Wei, Y., Wu, T., Yang, Y., Wang, H., Zong, H., Yang, J., Zhang, S., Xie, J., Kong, X., Liu, W., & Gu, J. (2006). Beta1,4-galactosyltransferase V functions as a positive growth regulator in glioma. Journal of Biological Chemistry, 281(14), 9482–9489.CrossRefPubMed Jiang, J., Chen, X., Shen, J., Wei, Y., Wu, T., Yang, Y., Wang, H., Zong, H., Yang, J., Zhang, S., Xie, J., Kong, X., Liu, W., & Gu, J. (2006). Beta1,4-galactosyltransferase V functions as a positive growth regulator in glioma. Journal of Biological Chemistry, 281(14), 9482–9489.CrossRefPubMed
go back to reference Kumagai, T., Sato, T., Natsuka, S., Kobayashi, Y., Zhou, D., Shinkai, T., & Hayakawa, S., & Furukawa, K. (2010). Involvement of murine β-1,4-galactosyltransferase V in lactosylceramide biosynthesis. Glycoconjugate Journal, 27(7–9), 685–695.CrossRefPubMedPubMedCentral Kumagai, T., Sato, T., Natsuka, S., Kobayashi, Y., Zhou, D., Shinkai, T., & Hayakawa, S., & Furukawa, K. (2010). Involvement of murine β-1,4-galactosyltransferase V in lactosylceramide biosynthesis. Glycoconjugate Journal, 27(7–9), 685–695.CrossRefPubMedPubMedCentral
go back to reference Liu, W., Vielhauer, G. A., Holzbeierlein, J. M., Zhao, H., Ghosh, S., Brown, D., Lee, E., & Blagg, B. S. (2015). KU675, a concomitant heat-shock protein inhibitor of Hsp90 and Hsc70 that manifests isoform selectivity for Hsp90α in prostate cancer cells. Molecular Pharmacology, 88(1), 121–130.CrossRefPubMedPubMedCentral Liu, W., Vielhauer, G. A., Holzbeierlein, J. M., Zhao, H., Ghosh, S., Brown, D., Lee, E., & Blagg, B. S. (2015). KU675, a concomitant heat-shock protein inhibitor of Hsp90 and Hsc70 that manifests isoform selectivity for Hsp90α in prostate cancer cells. Molecular Pharmacology, 88(1), 121–130.CrossRefPubMedPubMedCentral
go back to reference Ramp, U., Mahotka, C., Heikaus, S., Shibata, T., Grimm, M. O., Willers, R., & Gabbert, H. E. (2007). Expression of heat shock protein 70 in renal cell carcinoma and its relation to tumor progression and prognosis. Histology and Histopathology, 22(10), 1099–1107.PubMed Ramp, U., Mahotka, C., Heikaus, S., Shibata, T., Grimm, M. O., Willers, R., & Gabbert, H. E. (2007). Expression of heat shock protein 70 in renal cell carcinoma and its relation to tumor progression and prognosis. Histology and Histopathology, 22(10), 1099–1107.PubMed
go back to reference Robertson, T., Koszyca, B., & Gonzales, M. (2011). Overview and recent advances in neuropathology. Part 1: Central nervous system tumours. Pathology, 43(2), 88–92.CrossRefPubMed Robertson, T., Koszyca, B., & Gonzales, M. (2011). Overview and recent advances in neuropathology. Part 1: Central nervous system tumours. Pathology, 43(2), 88–92.CrossRefPubMed
go back to reference Shirane, K., Sato, T., Segawa, K., & Furukawa, K. (1999). Involvement of beta-1,4-galactosyltransferase V in malignant transformation-associated changes in glycosylation. Biochemical and Biophysical Research Communication, 265(2), 434–438.CrossRef Shirane, K., Sato, T., Segawa, K., & Furukawa, K. (1999). Involvement of beta-1,4-galactosyltransferase V in malignant transformation-associated changes in glycosylation. Biochemical and Biophysical Research Communication, 265(2), 434–438.CrossRef
go back to reference Tanaka, M., Mun, S., Harada, A., Ohkawa, Y., Inagaki, A., Sano, S., Takahashi, K., Izumi, Y., Osada-Oka, M., Wanibuchi, H., Yamagata, M., Yukimura, T., Miura, K., Shiota, M., & Iwao, H. (2014). Hsc70 contributes to cancer cell survival by preventing Rab1A degradation under stress conditions. PLoS ONE, 9(5), e96785.CrossRefPubMedPubMedCentral Tanaka, M., Mun, S., Harada, A., Ohkawa, Y., Inagaki, A., Sano, S., Takahashi, K., Izumi, Y., Osada-Oka, M., Wanibuchi, H., Yamagata, M., Yukimura, T., Miura, K., Shiota, M., & Iwao, H. (2014). Hsc70 contributes to cancer cell survival by preventing Rab1A degradation under stress conditions. PLoS ONE, 9(5), e96785.CrossRefPubMedPubMedCentral
go back to reference Vila-Carriles, W. H., Zhou, Z. H., Bubien, J. K., Fuller, C. M., & Benos, D. J. (2007). Participation of the chaperone Hsc70 in the trafficking and functional expression of ASIC2 in glioma cells. Journal of Biological Chemistry, 282(47), 34381–34391.CrossRefPubMed Vila-Carriles, W. H., Zhou, Z. H., Bubien, J. K., Fuller, C. M., & Benos, D. J. (2007). Participation of the chaperone Hsc70 in the trafficking and functional expression of ASIC2 in glioma cells. Journal of Biological Chemistry, 282(47), 34381–34391.CrossRefPubMed
go back to reference Wang, B. S., Yang, Y., Yang, H., Liu, Y. Z., Hao, J. J., Zhang, Y., Shi, Z. Z., Jia, X. M., Zhan, Q. M., & Wang, M. R. (2013). PKCι counteracts oxidative stress by regulating Hsc70 in an esophageal cancer cell line. Cell Stress and Chaperones, 18(3), 359–366.CrossRefPubMed Wang, B. S., Yang, Y., Yang, H., Liu, Y. Z., Hao, J. J., Zhang, Y., Shi, Z. Z., Jia, X. M., Zhan, Q. M., & Wang, M. R. (2013). PKCι counteracts oxidative stress by regulating Hsc70 in an esophageal cancer cell line. Cell Stress and Chaperones, 18(3), 359–366.CrossRefPubMed
Metadata
Title
Hsc70 Interacts with β4GalT5 to Regulate the Growth of Gliomas
Authors
Guan Sun
Ying Cao
Xueliang Dai
Min Li
Jun Guo
Publication date
01-03-2019
Publisher
Springer US
Published in
NeuroMolecular Medicine / Issue 1/2019
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI
https://doi.org/10.1007/s12017-018-08520-8

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