Abstract
BackgroundCoronins 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.ResultsThe 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.ConclusionCoronin 3 is highly expressed in gastric cancer metastases and can promote the metastatic behaviors of gastric cancer cells, including their migration and invasion.
Highlights
Coronins are a family of highly evolutionary conserved proteins reportedly involved in the regulation of actin cytoskeletal dynamics, only coronin 3 has been shown to be related to cancer cell migration
A tissue array containing 40 gastric cancer and related metastatic lymph lode tissues was purchased from Aomei, China, and another 12 pairs of tissue samples were obtained from archives of Department of Pathology in Xijing Hospital between 2010 and 2011
The immunohistochemical results showed that coronin 3 was predominantly expressed in the cytoplasm of gastric cancer cells (Figure 1A)
Summary
Coronins are a family of highly evolutionary conserved proteins reportedly involved in the regulation of actin cytoskeletal dynamics, only coronin 3 has been shown to be related to cancer cell migration. The knockdown of coronin 3 inhibits cell proliferation and invasion. 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. Cancer cell invasion during this process is dependent on the dynamic re-organization of the actin cytoskeleton, the dysfunction of cell adhesion, and the formation of invadopodia. Coronins are highly conserved regulators of the actin cytoskeleton, and their structure and biological function have recently been described in detail [6]. Coronin 3 is a novel biomarker for the invasive progression of hepatocellular carcinoma [11]
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