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Published in: Molecular Cancer 1/2012

Open Access 01-12-2012 | Research

Coronin 3 promotes gastric cancer metastasis via the up-regulation of MMP-9 and cathepsin K

Authors: Gui Ren, Qifei Tian, Yanxin An, Bin Feng, Yuanyuan Lu, Jie Liang, Kai Li, Yulong Shang, Yongzhan Nie, Xin Wang, Daiming Fan

Published in: Molecular Cancer | Issue 1/2012

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Abstract

Background

Coronins are a family of highly evolutionary conserved proteins reportedly involved in the regulation of actin cytoskeletal dynamics, although only coronin 3 has been shown to be related to cancer cell migration. In glioblastoma cells, the knockdown of coronin 3 inhibits cell proliferation and invasion. Coronin 3 is also associated with the aggression and metastasis of hepatocellular carcinoma. In this paper, we analyze the migration, invasion and metastasis abilities of gastric cancer cells after up- or down-regulation of coronin 3, and explore the mechanism of coronin 3 in the process of gastric cancer metastasis.

Results

The expression of coronin 3 was higher in the highly metastatic sub-cell line MKN28-M, which we established in our laboratory. We also demonstrated that the expression of coronin 3 was remarkably higher in lymph lode metastases than in primary gastric cancer tissues, and over-expression of coronin 3 was correlated with the increased clinical stage and lymph lode metastasis. Recombinant lentiviral vectors encoding shRNAs were designed to down-regulate coronin 3 expression in gastric cancer cell lines. Stable knockdown of coronin 3 by this lentiviral vector could efficiently inhibit the migration and invasion of MKN45 gastric cancer cells. In contrast, up-regulation of coronin 3 significantly enhanced migration and invasion of MKN28-NM cells. In addition, knockdown of coronin 3 significantly reduced liver metastasis in mice after tail vein injection of gastric cancer cells. The Human Tumor Metastasis PCR Array was used to screen the metastasis-associated genes identified by the down-regulation of coronin 3, and the results suggested that, following the knockdown of coronin 3, the tumor cell migration and invasion were inhibited by the reduced expression of MMP-9 and cathepsin K.

Conclusion

Coronin 3 is highly expressed in gastric cancer metastases and can promote the metastatic behaviors of gastric cancer cells, including their migration and invasion.
Appendix
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Literature
1.
go back to reference Gupta GP, Massague J: Cancer metastasis: building a framework. Cell. 2006, 127 (4): 679-695. 10.1016/j.cell.2006.11.001CrossRefPubMed Gupta GP, Massague J: Cancer metastasis: building a framework. Cell. 2006, 127 (4): 679-695. 10.1016/j.cell.2006.11.001CrossRefPubMed
2.
3.
go back to reference Yamaguchi H: Molecular mechanisms of invadopodium formation: the role of the N-WASP-Arp2/3 complex pathway and cofilin. J Cell Biol. 2005, 168 (3): 441-452. 10.1083/jcb.200407076PubMedCentralCrossRefPubMed Yamaguchi H: Molecular mechanisms of invadopodium formation: the role of the N-WASP-Arp2/3 complex pathway and cofilin. J Cell Biol. 2005, 168 (3): 441-452. 10.1083/jcb.200407076PubMedCentralCrossRefPubMed
4.
go back to reference Uetrecht AC, Bear JE: Coronins: the return of the crown. Trends Cell Biol. 2006, 16 (8): 421-426. 10.1016/j.tcb.2006.06.002CrossRefPubMed Uetrecht AC, Bear JE: Coronins: the return of the crown. Trends Cell Biol. 2006, 16 (8): 421-426. 10.1016/j.tcb.2006.06.002CrossRefPubMed
5.
go back to reference Kessels MM: Controlling actin cytoskeletal organization and dynamics during neuronal morphogenesis. Eur J Cell Biol. 2011, 90 (11): 926-933. 10.1016/j.ejcb.2010.08.011CrossRefPubMed Kessels MM: Controlling actin cytoskeletal organization and dynamics during neuronal morphogenesis. Eur J Cell Biol. 2011, 90 (11): 926-933. 10.1016/j.ejcb.2010.08.011CrossRefPubMed
6.
go back to reference Chan KT, Creed SJ, Bear JE: Unraveling the enigma: progress towards understanding the coronin family of actin regulators. Trends Cell Biol. 2011, 21 (8): 481-488. 10.1016/j.tcb.2011.04.004PubMedCentralCrossRefPubMed Chan KT, Creed SJ, Bear JE: Unraveling the enigma: progress towards understanding the coronin family of actin regulators. Trends Cell Biol. 2011, 21 (8): 481-488. 10.1016/j.tcb.2011.04.004PubMedCentralCrossRefPubMed
7.
go back to reference Nurnberg A, Kitzing T, Grosse R: Nucleating actin for invasion. Nat Rev Cancer. 2011, 11 (3): 177-187. 10.1038/nrc3003CrossRefPubMed Nurnberg A, Kitzing T, Grosse R: Nucleating actin for invasion. Nat Rev Cancer. 2011, 11 (3): 177-187. 10.1038/nrc3003CrossRefPubMed
8.
go back to reference Rybakin V, Clemen CS: Coronin proteins as multifunctional regulators of the cytoskeleton and membrane trafficking. Bio Essays. 2005, 27 (6): 625-632. Rybakin V, Clemen CS: Coronin proteins as multifunctional regulators of the cytoskeleton and membrane trafficking. Bio Essays. 2005, 27 (6): 625-632.
9.
go back to reference Luan S-L: Primary effusion lymphoma: genomic profiling revealed amplification of SELPLG and CORO1C encoding for proteins important for cell migration. J Pathol. 2010, 222 (2): 166-179. 10.1002/path.2752CrossRefPubMed Luan S-L: Primary effusion lymphoma: genomic profiling revealed amplification of SELPLG and CORO1C encoding for proteins important for cell migration. J Pathol. 2010, 222 (2): 166-179. 10.1002/path.2752CrossRefPubMed
10.
go back to reference Thal D: Expression of coronin-3 (coronin-1C) in diffuse gliomas is related to malignancy. J Pathol. 2008, 214 (4): 415-424.CrossRefPubMed Thal D: Expression of coronin-3 (coronin-1C) in diffuse gliomas is related to malignancy. J Pathol. 2008, 214 (4): 415-424.CrossRefPubMed
11.
go back to reference Wu L: Coronin-1C is a novel biomarker for hepatocellular carcinoma invasive progression identified by proteomics analysis and clinical validation. J Exp Clin Cancer Res. 2010, 29 (1): 17- 10.1186/1756-9966-29-17PubMedCentralCrossRefPubMed Wu L: Coronin-1C is a novel biomarker for hepatocellular carcinoma invasive progression identified by proteomics analysis and clinical validation. J Exp Clin Cancer Res. 2010, 29 (1): 17- 10.1186/1756-9966-29-17PubMedCentralCrossRefPubMed
12.
go back to reference Spoerl Z: Oligomerization, F-actin interaction, and membrane association of the ubiquitous mammalian coronin 3 are mediated by its carboxyl terminus. J Biol Chem. 2002, 277 (50): 48858-48867. 10.1074/jbc.M205136200CrossRefPubMed Spoerl Z: Oligomerization, F-actin interaction, and membrane association of the ubiquitous mammalian coronin 3 are mediated by its carboxyl terminus. J Biol Chem. 2002, 277 (50): 48858-48867. 10.1074/jbc.M205136200CrossRefPubMed
13.
14.
go back to reference Duffy MJ: Proteases as prognostic markers in cancer. Clin Cancer Res. 1996, 2 (4): 613-618.PubMed Duffy MJ: Proteases as prognostic markers in cancer. Clin Cancer Res. 1996, 2 (4): 613-618.PubMed
15.
go back to reference Cordes C: Simultaneous expression of Cathepsins B and K in pulmonary adenocarcinomas and squamous cell carcinomas predicts poor recurrence-free and overall survival. Lung Cancer. 2009, 64 (1): 79-85. 10.1016/j.lungcan.2008.07.005CrossRefPubMed Cordes C: Simultaneous expression of Cathepsins B and K in pulmonary adenocarcinomas and squamous cell carcinomas predicts poor recurrence-free and overall survival. Lung Cancer. 2009, 64 (1): 79-85. 10.1016/j.lungcan.2008.07.005CrossRefPubMed
16.
go back to reference Chambers AF, Groom AC, MacDonald IC: Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002, 2 (8): 563-572. 10.1038/nrc865CrossRefPubMed Chambers AF, Groom AC, MacDonald IC: Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002, 2 (8): 563-572. 10.1038/nrc865CrossRefPubMed
17.
18.
go back to reference Fernando HS, Kynaston HG, Jiang WG: WASP and WAVE proteins: Vital intrinsic regulators of cell motility and their role in cancer (Review). Int J Mol Med. 2009, 23 (2): 141-148.PubMed Fernando HS, Kynaston HG, Jiang WG: WASP and WAVE proteins: Vital intrinsic regulators of cell motility and their role in cancer (Review). Int J Mol Med. 2009, 23 (2): 141-148.PubMed
19.
20.
go back to reference Mullins RD, Heuser JA, Pollard TD: The interaction of Arp2/3 complex with actin: nucleation, high affinity pointed end capping, and formation of branching networks of filaments. Proc Natl Acad Sci USA. 1998, 95 (11): 6181-6186. 10.1073/pnas.95.11.6181PubMedCentralCrossRefPubMed Mullins RD, Heuser JA, Pollard TD: The interaction of Arp2/3 complex with actin: nucleation, high affinity pointed end capping, and formation of branching networks of filaments. Proc Natl Acad Sci USA. 1998, 95 (11): 6181-6186. 10.1073/pnas.95.11.6181PubMedCentralCrossRefPubMed
21.
go back to reference Cai L: Coronin 1B antagonizes cortactin and remodels Arp2/3-containing actin branches in lamellipodia. Cell. 2008, 134 (5): 828-842. 10.1016/j.cell.2008.06.054PubMedCentralCrossRefPubMed Cai L: Coronin 1B antagonizes cortactin and remodels Arp2/3-containing actin branches in lamellipodia. Cell. 2008, 134 (5): 828-842. 10.1016/j.cell.2008.06.054PubMedCentralCrossRefPubMed
22.
go back to reference Weaver AM: Cortactin promotes and stabilizes Arp2/3-induced actin filament network formation. Curr Biol. 2001, 11 (5): 370-3744. 10.1016/S0960-9822(01)00098-7CrossRefPubMed Weaver AM: Cortactin promotes and stabilizes Arp2/3-induced actin filament network formation. Curr Biol. 2001, 11 (5): 370-3744. 10.1016/S0960-9822(01)00098-7CrossRefPubMed
23.
go back to reference Rosentreter A: Coronin 3 involvement in F-actin-dependent processes at the cell cortex. Exp Cell Res. 2007, 313 (5): 878-895. 10.1016/j.yexcr.2006.12.015CrossRefPubMed Rosentreter A: Coronin 3 involvement in F-actin-dependent processes at the cell cortex. Exp Cell Res. 2007, 313 (5): 878-895. 10.1016/j.yexcr.2006.12.015CrossRefPubMed
24.
go back to reference Thal DR: Expression of coronin-3 (coronin-1C) in diffuse gliomas is related to malignancy. J Pathol. 2007, 214 (4): 415-424. 10.1002/path.2308.CrossRef Thal DR: Expression of coronin-3 (coronin-1C) in diffuse gliomas is related to malignancy. J Pathol. 2007, 214 (4): 415-424. 10.1002/path.2308.CrossRef
25.
go back to reference Wu L: Coronin-1C is a novel biomarker for hepatocellular carcinoma invasive progression identified by proteomics analysis and clinical validation. J Exp Clin Cancer Res. 2010, 29: 17- 10.1186/1756-9966-29-17PubMedCentralCrossRefPubMed Wu L: Coronin-1C is a novel biomarker for hepatocellular carcinoma invasive progression identified by proteomics analysis and clinical validation. J Exp Clin Cancer Res. 2010, 29: 17- 10.1186/1756-9966-29-17PubMedCentralCrossRefPubMed
26.
go back to reference Luan SL: Primary effusion lymphoma: genomic profiling revealed amplification of SELPLG and CORO1C encoding for proteins important for cell migration. J Pathol. 2010, 222 (2): 166-179. 10.1002/path.2752CrossRefPubMed Luan SL: Primary effusion lymphoma: genomic profiling revealed amplification of SELPLG and CORO1C encoding for proteins important for cell migration. J Pathol. 2010, 222 (2): 166-179. 10.1002/path.2752CrossRefPubMed
27.
go back to reference Sossey-Alaoui K: WAVE3 promotes cell motility and invasion through the regulation of MMP-1, MMP-3, and MMP-9 expression. Exp Cell Res. 2005, 308 (1): 135-145. 10.1016/j.yexcr.2005.04.011CrossRefPubMed Sossey-Alaoui K: WAVE3 promotes cell motility and invasion through the regulation of MMP-1, MMP-3, and MMP-9 expression. Exp Cell Res. 2005, 308 (1): 135-145. 10.1016/j.yexcr.2005.04.011CrossRefPubMed
28.
go back to reference Clark ES: Cortactin is an essential regulator of matrix metalloproteinase secretion and extracellular matrix degradation in invadopodia. Cancer Res. 2007, 67 (9): 4227-4235. 10.1158/0008-5472.CAN-06-3928CrossRefPubMed Clark ES: Cortactin is an essential regulator of matrix metalloproteinase secretion and extracellular matrix degradation in invadopodia. Cancer Res. 2007, 67 (9): 4227-4235. 10.1158/0008-5472.CAN-06-3928CrossRefPubMed
30.
go back to reference Nascimento CF: Role of MMP9 on invadopodia formation in cells from adenoid cystic carcinoma. Study by laser scanning confocal microscopy. Microscopy Research and Technique. 2010. Feb, 73 (2): 99-108.PubMed Nascimento CF: Role of MMP9 on invadopodia formation in cells from adenoid cystic carcinoma. Study by laser scanning confocal microscopy. Microscopy Research and Technique. 2010. Feb, 73 (2): 99-108.PubMed
31.
go back to reference Sossey-Alaoui K: WAVE3 promotes cell motility and invasion through the regulation of MMP-1, MMP-3, and MMP-9 expression. Exp Cell Res. 2005, 308 (1): 135-145. 10.1016/j.yexcr.2005.04.011CrossRefPubMed Sossey-Alaoui K: WAVE3 promotes cell motility and invasion through the regulation of MMP-1, MMP-3, and MMP-9 expression. Exp Cell Res. 2005, 308 (1): 135-145. 10.1016/j.yexcr.2005.04.011CrossRefPubMed
32.
go back to reference Tie J: MiR-218 inhibits invasion and metastasis of gastric cancer by targeting the Robo1 receptor. PLoS Genet. 2010, 6 (3): e1000879- 10.1371/journal.pgen.1000879PubMedCentralCrossRefPubMed Tie J: MiR-218 inhibits invasion and metastasis of gastric cancer by targeting the Robo1 receptor. PLoS Genet. 2010, 6 (3): e1000879- 10.1371/journal.pgen.1000879PubMedCentralCrossRefPubMed
33.
34.
go back to reference Zhang F: Identification of TRAK1 (Trafficking protein, kinesin-binding 1) as MGb2-Ag: A novel cancer biomarker. Cancer Lett. 2009, 274 (2): 250-258. 10.1016/j.canlet.2008.09.031CrossRefPubMed Zhang F: Identification of TRAK1 (Trafficking protein, kinesin-binding 1) as MGb2-Ag: A novel cancer biomarker. Cancer Lett. 2009, 274 (2): 250-258. 10.1016/j.canlet.2008.09.031CrossRefPubMed
35.
go back to reference Tang S: Overexpression of a novel gene gankyrin correlates with the malignant phenotype of colorectal cancer. Cancer Biol Ther. 2010, 9 (2): 88-95. 10.4161/cbt.9.2.10283CrossRefPubMed Tang S: Overexpression of a novel gene gankyrin correlates with the malignant phenotype of colorectal cancer. Cancer Biol Ther. 2010, 9 (2): 88-95. 10.4161/cbt.9.2.10283CrossRefPubMed
36.
go back to reference Jin H: p75 neurotrophin receptor inhibits invasion and metastasis of gastric cancer. Mol Cancer Res. 2007, 5 (5): 423-433. 10.1158/1541-7786.MCR-06-0407CrossRefPubMed Jin H: p75 neurotrophin receptor inhibits invasion and metastasis of gastric cancer. Mol Cancer Res. 2007, 5 (5): 423-433. 10.1158/1541-7786.MCR-06-0407CrossRefPubMed
Metadata
Title
Coronin 3 promotes gastric cancer metastasis via the up-regulation of MMP-9 and cathepsin K
Authors
Gui Ren
Qifei Tian
Yanxin An
Bin Feng
Yuanyuan Lu
Jie Liang
Kai Li
Yulong Shang
Yongzhan Nie
Xin Wang
Daiming Fan
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2012
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-11-67

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