Ion channel TRPML2 (MCOLN2) promotes ovarian cancer metastasis and chemoresistance.

BACKGROUND

Ovarian cancer, with metastasis and chemoresistance being the major obstacles to successful treatment, is a leading cause of death among gynecological malignancies. Identifying new molecular targets and understanding the underlying mechanisms of metastasis and chemoresistance are pressing issues in ovarian cancer therapy. Emerging evidence suggests that an endolysosomal Ca2+-permeable channel TRPML2 may contribute to cancer progression. However, its exact role and associated underlying mechanisms in ovarian cancer remain largely unknown.

METHODS

TRPML2 expression was studied by tissue and cellular immunostaining and western blots. The functional role of TRPML2 in cancer was assessed by cell viability assay, colony-formation assay, wound-healing assay and transwell assay. The resistance to carboplatin-induced cytotoxic effects was evaluated by Cell Counting Kit-8.

RESULTS

The TRPML2 expression is elevated in ovarian cancer cell lines and ovarian tumor tissues with high expression predicting a poor prognosis in ovarian cancer. TRPML2 knockdown with siRNA markedly reduced the proliferation of ovarian cancer cells, decreased the colony formation and migration, and increased the sensitivity of ovarian cancer cells to a chemoresistant drug carboplatin.

CONCLUSION

In summary, TRPML2 is critically involved in ovarian cancer progression and chemoresistance to carboplatin. Our study highlights an exciting possibility of targeting TRPML2 as a potential therapeutic option.