Cortactin contributes to the tumorigenicity of colorectal cancer by promoting cell proliferation

Abstract

Cortactin is a scaffolding protein that regulates Arp2/3-mediated actin polymerization. We showed in a previous study that cortactin was highly expressed in human stage II-III colorectal cancer (CRC) tissues. In the present study, using colony formation and CCK-8 assays, we showed that overexpression of cortactin accelerated the proliferation of CRC cells. Flow cytometric assays revealed that cortactin promoted G1/S phase cell cycle transition. Later, we constructed the phosphorylation mutation of cortactin at the Tyr421 residue. Colony formation and CCK-8 assays showed that cortactin/Tyr421A lost its ability to promote cell proliferation. Western blot analysis indicated that cortactin activated cyclin D1, but not cortactin/Tyr421A. Further study in nude mice revealed that there was a greater decrease in both tumor volume and tumor weight in animals injected with SW480/cortactin/Tyr421A cells than in those injected with SW480/cortactin/WT cells. Thus, the present study demonstrates that the cortactin Tyr421 residue is required to promote cell proliferation both in vitro and in vivo.

NDRG3 facilitates colorectal cancer metastasis through activating Src phosphorylation

“…Subcutaneous tumor formation experiment was performed as previously described. 19 The experiment was performed according to the Guide for the Care and Use Laboratory Animals of Ruijin Hospital, Shanghai Jiaotong University School of Medicine. Ethics committee of Ruijin Hospital also approved this research for using animals.…”

Binding of USP4 to cortactin enhances cell migration in HCT116 human colon cancer cells

“…It was reported that USP4 and CTTN are highly correlated with metastasis and poor survival rate in colon cancers, suggesting that they are possibly involved in cell migration. For example, the USP4 knockdown in colorectal cancer cells, SW480 and HCT116, reduced migration and invasion activity 32 ; the expression of CTTN was upregulated in metastatic colorectal cancer patients and in highly invasive colorectal cell lines, SW1116, SW480, and SW620; the high CTTN expression in colorectal cancer patients showed short survival; the expression level of CTTN in SW480 and SW620 cells was positively correlated with cell migration and invasion 22,33 . Therefore, we can propose that the functions of USP4‐CTTN axis on cell migration might be commonly observed in colon cancer cell lines.…”

“…For example, the USP4 knockdown in colorectal cancer cells, SW480 and HCT116, reduced migration and invasion activity 32 ; the expression of CTTN was upregulated in metastatic colorectal cancer patients and in highly invasive colorectal cell lines, SW1116, SW480, and SW620; the high CTTN expression in colorectal cancer patients showed short survival; the expression level of CTTN in SW480 and SW620 cells was positively correlated with cell migration and invasion. 22,33 Therefore, we can propose that the functions of USP4-CTTN axis on cell migration might be commonly observed in colon cancer cell lines. However, further study is needed to prove the role of USP4-CTTN in other colon cancers or other types of cancer.…”

Hematopoietic lineage cell-specific protein 1 (HS1), a hidden player in migration, invasion, and tumor formation, is over-expressed in ovarian carcinoma cells

“…Then, we focused on HS1 due to its homology with CTTN. Many reports have demonstrated the contribution of CTTN to cell migration and invasion in solid tumors [ 8 – 10 , 13 ]. HS1 and CTTN have very similar intracellular structures and functions.…”

“…CTTN binds to the Arp2/3 complex and promotes actin assembly by helping to form and stabilize actin filament branches. It has also been reported that CTTN is associated with tumor progression and poor prognosis in many malignancies [ 13 – 15 ].…”