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Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Research

P-cadherin counteracts myosin II-B function: implications in melanoma progression

Authors: Koen Jacobs, Mireille Van Gele, Ramses Forsyth, Lieve Brochez, Barbara Vanhoecke, Olivier De Wever, Marc Bracke

Published in: Molecular Cancer | Issue 1/2010

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Abstract

Background

Malignant transformation of melanocytes is frequently attended by a switch in cadherin expression profile as shown for E- and N-cadherin. For P-cadherin, downregulation in metastasizing melanoma has been demonstrated, and over-expression of P-cadherin in melanoma cell lines has been shown to inhibit invasion. The strong invasive and metastatic nature of cutaneous melanoma implies a deregulated interplay between intercellular adhesion and migration-related molecules

Results

In this study we performed a microarray analysis to compare the mRNA expression profile of an invasive BLM melanoma cell line (BLM LIE) and the non-invasive P-cadherin over-expression variant (BLM P-cad). Results indicate that nonmuscle myosin II-B is downregulated in BLM P-cad. Moreover, myosin II-B plays a major role in melanoma migration and invasiveness by retracting the tail during the migratory cycle, as shown by the localization of myosin II-B stress fibers relative to Golgi and the higher levels of phosphorylated myosin light chain. Analysis of P-cadherin and myosin II-B in nodular melanoma sections and in a panel of melanoma cell lines further confirmed that there is an inverse relationship between both molecules.

Conclusions

Therefore, we conclude that P-cadherin counteracts the expression and function of myosin II-B, resulting in the suppression of the invasive and migratory behaviour of BLM melanoma cells
Appendix
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Literature
1.
go back to reference Geller AC, Swetter SM, Brooks K, Demierre MF, Yaroch AL: Screening, early detection, and trends for melanoma: Current status (2000-2006) and future directions. J Am Acad Dermatol. 2007, 57 (4): 555-572. 10.1016/j.jaad.2007.06.032CrossRefPubMed Geller AC, Swetter SM, Brooks K, Demierre MF, Yaroch AL: Screening, early detection, and trends for melanoma: Current status (2000-2006) and future directions. J Am Acad Dermatol. 2007, 57 (4): 555-572. 10.1016/j.jaad.2007.06.032CrossRefPubMed
2.
go back to reference Geller AC, Annas GD: Epidemiology of melanoma and nonmelanoma skin cancer. Semin Oncol Nurs. 2003, 19: 2-11. 10.1053/sonu.2003.50000CrossRefPubMed Geller AC, Annas GD: Epidemiology of melanoma and nonmelanoma skin cancer. Semin Oncol Nurs. 2003, 19: 2-11. 10.1053/sonu.2003.50000CrossRefPubMed
3.
go back to reference Valyi-Nagy IT, Hirka G, Jensen PJ, Shih IM, Juhasz I, Herlyn M: Undifferentiated keratinocytes control growth, morphology, and antigen expression of normal melanocytes through cell-cell contact. Lab Invest. 1993, 69: 152-159.PubMed Valyi-Nagy IT, Hirka G, Jensen PJ, Shih IM, Juhasz I, Herlyn M: Undifferentiated keratinocytes control growth, morphology, and antigen expression of normal melanocytes through cell-cell contact. Lab Invest. 1993, 69: 152-159.PubMed
4.
go back to reference Mei-Yu Hsu, Meier FE, Nesbit M, Ju-Yu Hsu, Van Belle P, Elder DE, Herlyn M: E-Cadherin expression in melanoma cells restores keratinocyte-mediated growth control and down-regulates expression of invasion-related adhesion receptors. Am J Pathol. 2000, 156: 1515-1525.CrossRef Mei-Yu Hsu, Meier FE, Nesbit M, Ju-Yu Hsu, Van Belle P, Elder DE, Herlyn M: E-Cadherin expression in melanoma cells restores keratinocyte-mediated growth control and down-regulates expression of invasion-related adhesion receptors. Am J Pathol. 2000, 156: 1515-1525.CrossRef
5.
go back to reference Stetler-Stevenson WG, Yu AE: Proteases in invasion: matrix metalloproteinases. Semin Cancer Biol. 2001, 11 (2): 143-152. 10.1006/scbi.2000.0365CrossRefPubMed Stetler-Stevenson WG, Yu AE: Proteases in invasion: matrix metalloproteinases. Semin Cancer Biol. 2001, 11 (2): 143-152. 10.1006/scbi.2000.0365CrossRefPubMed
6.
go back to reference Wheelock MJ, Johnson KR: Cadherines as modulators of cellular phenotype. Annu Rev Cell Dev Biol. 2003, 19: 207-235. 10.1146/annurev.cellbio.19.011102.111135CrossRefPubMed Wheelock MJ, Johnson KR: Cadherines as modulators of cellular phenotype. Annu Rev Cell Dev Biol. 2003, 19: 207-235. 10.1146/annurev.cellbio.19.011102.111135CrossRefPubMed
7.
go back to reference Bracke ME, Van Roy FM, Mareel MM: The E-cadherin/catenin complex in invasion and metastasis. Curr Top Microbiol Immunol. 1996, 213: 123-161.PubMed Bracke ME, Van Roy FM, Mareel MM: The E-cadherin/catenin complex in invasion and metastasis. Curr Top Microbiol Immunol. 1996, 213: 123-161.PubMed
8.
go back to reference Paredes J, Correia AL, Ribeiro AS, Albergaria A, Milanezi F, Schmitt FC: P-cadherin in breast cancer: a review. Breast Cancer Research. 2007, 9: 214-226. 10.1186/bcr1774PubMedCentralCrossRefPubMed Paredes J, Correia AL, Ribeiro AS, Albergaria A, Milanezi F, Schmitt FC: P-cadherin in breast cancer: a review. Breast Cancer Research. 2007, 9: 214-226. 10.1186/bcr1774PubMedCentralCrossRefPubMed
9.
go back to reference Foty RA, Steinberg MS: Measurement of tumor cell cohesion and suppression of invasion by E- or P-cadherin. Cancer Res. 1997, 57 (22): 5033-5036.PubMed Foty RA, Steinberg MS: Measurement of tumor cell cohesion and suppression of invasion by E- or P-cadherin. Cancer Res. 1997, 57 (22): 5033-5036.PubMed
10.
go back to reference Jarrard DF: P-cadherin is a basal cell-specific epithelial marker that is not expressed in prostate cancer. Clin Cancer Res. 1997, 3: 2121-2128.PubMed Jarrard DF: P-cadherin is a basal cell-specific epithelial marker that is not expressed in prostate cancer. Clin Cancer Res. 1997, 3: 2121-2128.PubMed
11.
go back to reference Peinado H, Olmeda D, Cano A: Snail, Zeb and bHLH in tumour progression: an alliance against the epithelial phenotype?. Nat Rev Cancer. 2007, 7 (6): 415-428. 10.1038/nrc2131CrossRefPubMed Peinado H, Olmeda D, Cano A: Snail, Zeb and bHLH in tumour progression: an alliance against the epithelial phenotype?. Nat Rev Cancer. 2007, 7 (6): 415-428. 10.1038/nrc2131CrossRefPubMed
12.
go back to reference Van Marck V, Stove C, Van Den Bossche K, Stove V, Paredes J, Vander Haeghen Y, Bracke M: P-cadherin promotes cell-cell adhesion and counteracts invasion in human melanoma. Cancer Res. 2005, 65: 8774-8783. 10.1158/0008-5472.CAN-04-4414CrossRefPubMed Van Marck V, Stove C, Van Den Bossche K, Stove V, Paredes J, Vander Haeghen Y, Bracke M: P-cadherin promotes cell-cell adhesion and counteracts invasion in human melanoma. Cancer Res. 2005, 65: 8774-8783. 10.1158/0008-5472.CAN-04-4414CrossRefPubMed
13.
go back to reference Paredes J, Stove C, Stove V, Milanezi F, Van Marck V, Derycke L, Mareel M, Bracke M, Schmitt F: P-cadherin is up-regulated by the antiestrogen ICI 182, 780 and promotes invasion of human breast cancer cells. Cancer Res. 2004, 64 (22): 8309-8317. 10.1158/0008-5472.CAN-04-0795CrossRefPubMed Paredes J, Stove C, Stove V, Milanezi F, Van Marck V, Derycke L, Mareel M, Bracke M, Schmitt F: P-cadherin is up-regulated by the antiestrogen ICI 182, 780 and promotes invasion of human breast cancer cells. Cancer Res. 2004, 64 (22): 8309-8317. 10.1158/0008-5472.CAN-04-0795CrossRefPubMed
14.
go back to reference Taniuchi K, Nakagawa H, Hosokawa M, Nakamura T, Eguchi H, Ohigashi H, Ishikawa O, Katagiri T, Nakamura Y: Overexpressed P-cadherin/CDH3 promotes motility of pancreatic cancer cells by interacting with p120ctn and activating rho-family GTPases. Cancer Res. 2005, 65 (8): 3092-3099.PubMed Taniuchi K, Nakagawa H, Hosokawa M, Nakamura T, Eguchi H, Ohigashi H, Ishikawa O, Katagiri T, Nakamura Y: Overexpressed P-cadherin/CDH3 promotes motility of pancreatic cancer cells by interacting with p120ctn and activating rho-family GTPases. Cancer Res. 2005, 65 (8): 3092-3099.PubMed
15.
go back to reference Sellers JR: Myosins: a diverse superfamily. Mol Cell Res. 2000, 1496 (1): 3-22. Sellers JR: Myosins: a diverse superfamily. Mol Cell Res. 2000, 1496 (1): 3-22.
16.
go back to reference Bresnick AR: Molecular mechanisms of nonmuscle myosin II regulation. Curr Opin Cell Biol. 1999, 11: 26-33. 10.1016/S0955-0674(99)80004-0CrossRefPubMed Bresnick AR: Molecular mechanisms of nonmuscle myosin II regulation. Curr Opin Cell Biol. 1999, 11: 26-33. 10.1016/S0955-0674(99)80004-0CrossRefPubMed
17.
go back to reference Swailes NT, Colegrave M, Knight PJ, Peckham M: Nonmuscle myosin 2A and 2B drive changes in cell morphology that occur as myoblasts align and fuse. J Cell Sci. 2006, 119: 3561-3570. 10.1242/jcs.03096CrossRefPubMed Swailes NT, Colegrave M, Knight PJ, Peckham M: Nonmuscle myosin 2A and 2B drive changes in cell morphology that occur as myoblasts align and fuse. J Cell Sci. 2006, 119: 3561-3570. 10.1242/jcs.03096CrossRefPubMed
18.
go back to reference Kolega J: Asymmetric distribution of myosin IIB in migrating endothelial cells is regulated by a rho-dependent kinase and contributes to tail retraction. Mol Biol Cell. 2003, 14: 4745-4757. 10.1091/mbc.E03-04-0205PubMedCentralCrossRefPubMed Kolega J: Asymmetric distribution of myosin IIB in migrating endothelial cells is regulated by a rho-dependent kinase and contributes to tail retraction. Mol Biol Cell. 2003, 14: 4745-4757. 10.1091/mbc.E03-04-0205PubMedCentralCrossRefPubMed
19.
go back to reference Vicente-Manzanares M, Koach MA, Whitmore L, Lamers ML, Horwitz AF: Segregation and activation of myosin IIB creates a rear in migrating cells. J Cell Biol. 2008, 183 (3): 543-554. 10.1083/jcb.200806030PubMedCentralCrossRefPubMed Vicente-Manzanares M, Koach MA, Whitmore L, Lamers ML, Horwitz AF: Segregation and activation of myosin IIB creates a rear in migrating cells. J Cell Biol. 2008, 183 (3): 543-554. 10.1083/jcb.200806030PubMedCentralCrossRefPubMed
20.
go back to reference Rochlin MW, Itoh K, Adelstein RS, Bridgeman PC: Localization of Myosin IIA and B isoforms in cultured neurons. J Cell Sci. 1995, 108: 3661-3670.PubMed Rochlin MW, Itoh K, Adelstein RS, Bridgeman PC: Localization of Myosin IIA and B isoforms in cultured neurons. J Cell Sci. 1995, 108: 3661-3670.PubMed
21.
go back to reference Yamakita Y, Yamashiro S, Matsumura F: In vivo phosphorylation of regulatory light chain of myosin II during mitosis of cultured cell. J Cell Biol. 1994, 124: 129-137. 10.1083/jcb.124.1.129CrossRefPubMed Yamakita Y, Yamashiro S, Matsumura F: In vivo phosphorylation of regulatory light chain of myosin II during mitosis of cultured cell. J Cell Biol. 1994, 124: 129-137. 10.1083/jcb.124.1.129CrossRefPubMed
22.
go back to reference Amano M, Ito M, Kimura K, Fukata Y, Chihara K, Nakano T, Matsuura Y, Kaibuchi K: Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J Biol Chem. 1996, 271 (34): 20246-20249. 10.1074/jbc.271.34.20246CrossRefPubMed Amano M, Ito M, Kimura K, Fukata Y, Chihara K, Nakano T, Matsuura Y, Kaibuchi K: Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J Biol Chem. 1996, 271 (34): 20246-20249. 10.1074/jbc.271.34.20246CrossRefPubMed
23.
go back to reference Matsumura F, Shoichiro O, Go T, Yamashiro S: Specific localization of serine 19 phosphorylated myosin II during cell locomotion and mitosis of cultured cells. J Cell Biol. 1998, 140 (1): 119-129. 10.1083/jcb.140.1.119PubMedCentralCrossRefPubMed Matsumura F, Shoichiro O, Go T, Yamashiro S: Specific localization of serine 19 phosphorylated myosin II during cell locomotion and mitosis of cultured cells. J Cell Biol. 1998, 140 (1): 119-129. 10.1083/jcb.140.1.119PubMedCentralCrossRefPubMed
24.
go back to reference Sanders DSA, Blessing K, Hassan GAR, Bruton R, Marsden JR, Jankowski J: Alterations in cadherin and catenin expression during the biological progression of melanocytic tumours. Mol Pathol. 1999, 52: 151-157. 10.1136/mp.52.3.151PubMedCentralCrossRefPubMed Sanders DSA, Blessing K, Hassan GAR, Bruton R, Marsden JR, Jankowski J: Alterations in cadherin and catenin expression during the biological progression of melanocytic tumours. Mol Pathol. 1999, 52: 151-157. 10.1136/mp.52.3.151PubMedCentralCrossRefPubMed
25.
go back to reference Hsu MY, Wheelock MJ, Johnson KR, Herlyn M: Shifts in cadherin profiles between human normal melanocytes and melanomas. J Invest Dermatol Symp Proc. 1996, 1: 188-194. Hsu MY, Wheelock MJ, Johnson KR, Herlyn M: Shifts in cadherin profiles between human normal melanocytes and melanomas. J Invest Dermatol Symp Proc. 1996, 1: 188-194.
26.
go back to reference Noren NK, Niessen CM, Gumbiner BM, Burridge K: Cadherin engagement regulates Rho family GTPases. J Biol Chem. 2001, 267: 33305-33308. 10.1074/jbc.C100306200.CrossRef Noren NK, Niessen CM, Gumbiner BM, Burridge K: Cadherin engagement regulates Rho family GTPases. J Biol Chem. 2001, 267: 33305-33308. 10.1074/jbc.C100306200.CrossRef
27.
go back to reference Navarro C, Nola S, Audebert S, Santoni MJ, Arsanto JP, Ginestier C, Marchetto S, Jacquemier J, Isnardon D, Le Bivic A, Birnbaum D, Borg JP: Junctional recruitment of mammalian Scribble relies on E-cadherin engagement. Oncogene. 2005, 24 (27): 3725-3730. 10.1038/sj.onc.1208632.CrossRef Navarro C, Nola S, Audebert S, Santoni MJ, Arsanto JP, Ginestier C, Marchetto S, Jacquemier J, Isnardon D, Le Bivic A, Birnbaum D, Borg JP: Junctional recruitment of mammalian Scribble relies on E-cadherin engagement. Oncogene. 2005, 24 (27): 3725-3730. 10.1038/sj.onc.1208632.CrossRef
28.
go back to reference Montgomery AM, Becker JC, Siu CH, Lemmon VP, Cheresh DA, Pancook JD, Zhao X, Reisfeld RA: Human neural cell adhesion molecule L1 and rat homologue NILE are ligands for integrin alpha v beta 3. J Cell Biol. 1996, 132: 475-485. 10.1083/jcb.132.3.475CrossRefPubMed Montgomery AM, Becker JC, Siu CH, Lemmon VP, Cheresh DA, Pancook JD, Zhao X, Reisfeld RA: Human neural cell adhesion molecule L1 and rat homologue NILE are ligands for integrin alpha v beta 3. J Cell Biol. 1996, 132: 475-485. 10.1083/jcb.132.3.475CrossRefPubMed
29.
go back to reference Mei-Yu Hsu, Meier FE, Nesbit M, Ju-Yu Hsu, Van Belle P, Elder DE, Herlyn ME: -cadherin expression in melanoma cells restores keratinocyte-mediated growth control and downregulates expression of invasion-related adhesion receptors. Am J Pathol. 2000, 156: 1515-1525.CrossRef Mei-Yu Hsu, Meier FE, Nesbit M, Ju-Yu Hsu, Van Belle P, Elder DE, Herlyn ME: -cadherin expression in melanoma cells restores keratinocyte-mediated growth control and downregulates expression of invasion-related adhesion receptors. Am J Pathol. 2000, 156: 1515-1525.CrossRef
30.
go back to reference Hsu M, Andl T, Li G, Meinkoth JL, Herlyn M: Cadherin repertoire determines partner-specific gap junctional communication during melanoma progression. J cell Sci. 2000, 113: 1535-1542.PubMed Hsu M, Andl T, Li G, Meinkoth JL, Herlyn M: Cadherin repertoire determines partner-specific gap junctional communication during melanoma progression. J cell Sci. 2000, 113: 1535-1542.PubMed
31.
go back to reference Sandig M, Voura EB, Kalnins VI, Siu CH: Role of cadherins in the transendothelial migration of melanoma cells in culture. Cell Motil Cytoskeleton. 1997, 38: 351-364. 10.1002/(SICI)1097-0169(1997)38:4<351::AID-CM5>3.0.CO;2-6CrossRefPubMed Sandig M, Voura EB, Kalnins VI, Siu CH: Role of cadherins in the transendothelial migration of melanoma cells in culture. Cell Motil Cytoskeleton. 1997, 38: 351-364. 10.1002/(SICI)1097-0169(1997)38:4<351::AID-CM5>3.0.CO;2-6CrossRefPubMed
32.
go back to reference Dupin E, Le Douarin NM: Development of melanocyte precursors from the vertebrate neural crest. Oncogene. 2003, 22: 3016-3023. 10.1038/sj.onc.1206460CrossRefPubMed Dupin E, Le Douarin NM: Development of melanocyte precursors from the vertebrate neural crest. Oncogene. 2003, 22: 3016-3023. 10.1038/sj.onc.1206460CrossRefPubMed
33.
34.
go back to reference Alder J, Zheng JQ: Surfing on calcium waves. Neuron. 2007, 54: 502-505. 10.1016/j.neuron.2007.04.024CrossRefPubMed Alder J, Zheng JQ: Surfing on calcium waves. Neuron. 2007, 54: 502-505. 10.1016/j.neuron.2007.04.024CrossRefPubMed
35.
go back to reference Shengyu Yang, Xin-Yun Huang: Ca2+ influx through L-type Ca2+ channels controls the trailing tail contraction in growth factor-induced fibroblast cell migration. J Biol Chem. 2005, 280: 27130-37. 10.1074/jbc.M501625200CrossRef Shengyu Yang, Xin-Yun Huang: Ca2+ influx through L-type Ca2+ channels controls the trailing tail contraction in growth factor-induced fibroblast cell migration. J Biol Chem. 2005, 280: 27130-37. 10.1074/jbc.M501625200CrossRef
36.
go back to reference Husi H, Ward MA, Choudhary JS, Blackstock WP, Grant SGN: Proteomic analysis of NMDA receptor-adhesion protein signaling complex. Nat Neuroscience. 2000, 3: 661-669. 10.1038/76615.CrossRefPubMed Husi H, Ward MA, Choudhary JS, Blackstock WP, Grant SGN: Proteomic analysis of NMDA receptor-adhesion protein signaling complex. Nat Neuroscience. 2000, 3: 661-669. 10.1038/76615.CrossRefPubMed
37.
go back to reference Komuro H, Kumada T: Ca2+ transients control CNS neuronal migration. Cell Calcium. 2000, 37: 387-393. 10.1016/j.ceca.2005.01.006.CrossRef Komuro H, Kumada T: Ca2+ transients control CNS neuronal migration. Cell Calcium. 2000, 37: 387-393. 10.1016/j.ceca.2005.01.006.CrossRef
38.
go back to reference Van Gele M, Geusens B, Schmitt AM, Aguilar L, Lambert J: Knockdown of myosin Vaisoforms by RNAi as a tool to block melanosome transportin primary human melanocytes. J Invest Dermatol. 2008, 128: 2474-2484. 10.1038/jid.2008.100CrossRefPubMed Van Gele M, Geusens B, Schmitt AM, Aguilar L, Lambert J: Knockdown of myosin Vaisoforms by RNAi as a tool to block melanosome transportin primary human melanocytes. J Invest Dermatol. 2008, 128: 2474-2484. 10.1038/jid.2008.100CrossRefPubMed
39.
go back to reference Vandesompele J, De Paepe A, Speleman F: Elimination of primer-dimer artifacts and genomic coamplification using a two-step SYBR green I real-time RT-PCR. Anal biochem. 2002, 303: 95-98. 10.1006/abio.2001.5564CrossRefPubMed Vandesompele J, De Paepe A, Speleman F: Elimination of primer-dimer artifacts and genomic coamplification using a two-step SYBR green I real-time RT-PCR. Anal biochem. 2002, 303: 95-98. 10.1006/abio.2001.5564CrossRefPubMed
40.
go back to reference Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe E, Speleman F: Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002, 3: RESEARCH0034- 10.1186/gb-2002-3-7-research0034PubMedCentralCrossRefPubMed Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe E, Speleman F: Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002, 3: RESEARCH0034- 10.1186/gb-2002-3-7-research0034PubMedCentralCrossRefPubMed
Metadata
Title
P-cadherin counteracts myosin II-B function: implications in melanoma progression
Authors
Koen Jacobs
Mireille Van Gele
Ramses Forsyth
Lieve Brochez
Barbara Vanhoecke
Olivier De Wever
Marc Bracke
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-255

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