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

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.

• Authors: Gui Ren, Qifei Tian, Yanxin An, Bin Feng, Yuanyuan Lu, Jie Liang, Kai Li, Yulong Shang, Yongzhan Nie, Xin Wang, Daiming Fan
• Journal: Molecular cancer (Mol Cancer) Vol. 11 Pg. 67 (Sep 14 2012) ISSN: 1476-4598 [Electronic] England
• PMID: 22974233 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Microfilament Proteins
• coronin proteins
• Cathepsin K
• Matrix Metalloproteinase 9

Topics

• Animals
• Cathepsin K (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (genetics)
• Cytoplasm (metabolism)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Mice
• Mice, Nude
• Microfilament Proteins (genetics, metabolism)
• Neoplasm Metastasis
• Protein Transport
• RNA Interference
• Stomach Neoplasms (genetics, metabolism, pathology)