e12600 Background: To further investigate the role of CMTM6 in breast cancer radiosensitivity, this study employed lentivirus-mediated gene overexpression/knockdown techniques to construct breast cancer cell lines with CMTM6 overexpression or knockdown. The effects of different CMTM6 expression levels on breast cancer cell proliferation, migration, and invasion capabilities were validated, along with its impact on radiosensitivity and underlying mechanisms. The aim is to explore the molecular mechanisms of CMTM6 in breast cancer radiosensitivity, identify new therapeutic targets, and provide more effective treatment strategies for breast cancer patients. Methods: Firstly, we established and validated CMTM6-overexpressing/knockdown breast cancer cell lines, and investigated the effects of CMTM6 overexpression/knockdown on the proliferation, migration, and invasion of breast cancer cells, as well as on these cellular behaviors after irradiation. After treating control and CMTM6-knockdown MDA-MB-231 cells with 4 Gy irradiation, Western blot assays were conducted to explore the effect of CMTM6 on DNA damage in breast cancer cells after irradiation. Respectively, followed by Western blot analysis to detect the expression levels of proteins related to the JAK2/STAT3 signaling pathway, aiming to elucidate the mechanism of CMTM6 in breast cancer cell radiosensitivity. Results: The protein expression level of CMTM6 in CMTM6-knockdown MDA-MB-231 cells was significantly lower than that in the non-knockdown group. Meanwhile, qRT-PCR detection revealed that the mRNA expression level of CMTM6 was significantly reduced in CMTM6-knockdown MDA-MB-231 cells. In contrast, the protein expression level of CMTM6 was significantly increased in CMTM6-overexpressing MCF7 cells compared to the empty vector group. CMTM6 knockdown inhibited the proliferation, migration, and invasion abilities of breast cancer cells after irradiation. Conversely, CMTM6 overexpression promoted the proliferation and migration of irradiated cells and reduced the radiosensitivity of breast cancer cells. Knocking down CMTM6 may enhance the radiosensitivity of MDA-MB-231 cells by inhibiting the activation of the JAK2/STAT3 signaling pathway. Conclusions: This study demonstrates significant differences in CMTM6 expression levels across different breast cancer cell lines. CMTM6 plays an important role in breast cancer proliferation, migration, invasion, and radiosensitivity. Modulating CMTM6 expression can influence the biological behavior of cancer cells: knockdown of CMTM6 significantly inhibits the proliferation, migration, and invasion abilities of MDA-MB-231 cells, while overexpression of CMTM6 significantly promotes the proliferation and migration of MCF7 cells. Furthermore, knockdown of CMTM6 may enhance the radiosensitivity of breast cancer cells by inhibiting the activation of the JAK2/STAT3 signaling pathway.
Sisi He (Thu,) studied this question.