CHCHD2 decreases docetaxel sensitivity in breast cancer via activating MMP2

L. Ma, L.-H. Zheng, D.-G. Zhang, Z.-M. Fan

Department of Breast Surgery, the First Hospital of Jilin University, Changchun, China. 234591611@qq.com

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• Pharmacology

OBJECTIVE: This study aims to clarify the influences of CHCHD2 and MMP2 on docetaxel resistance in breast cancer.

PATIENTS AND METHODS: Differential levels of CHCHD2 in breast cancer and para-tumor tissues were detected. The relationship between CHCHD2 and prognosis in breast cancer patients was analyzed. After generating Docetaxel-resistant breast cancer cell lines (MCF-7/DTX and SKBR3/DTX), the regulatory effects of CHCHD2 on proliferative and migratory potentials were assessed by Cell Counting Kit-8 (CCK-8) and transwell assay, respectively. The interaction between CHCHD2 and MMP2 was tested by Western blot and Pearson correlation test. At last, the involvement of MMP2 in CHCHD2-regulated proliferation and migration in Docetaxel-resistant breast cancer cells was analyzed.

RESULTS: CHCHD2 was upregulated in breast cancer tissues. It predicted high incidence of distant metastasis and poor prognosis in breast cancer patients. Proliferation inhibition rate was lower in MCF-7/DTX and SKBR3/DTX cells compared with their parental cells. After knockdown of CHCHD2 in MCF-7/DTX and SKBR3/DTX cells, their proliferative and migratory potentials were markedly reduced. MMP2 was upregulated in breast cancer tissues, and its level was positively regulated by CHCHD2. Overexpression of MMP2 could reverse the regulatory effects of CHCHD2 on proliferative and migratory potentials in MCF-7/DTX and SKBR3/DTX cells.

CONCLUSIONS: Upregulated CHCHD2 in breast cancer is related to distant metastasis rate and poor prognosis. CHCHD2 and MMP2 are positively correlated to each other. CHCHD2 stimulates proliferative and migratory potentials in Docetaxel-resistant breast cancer cells by upregulating MMP2.

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