FGF13 enhances resistance to platinum drugs by regulating hCTR1 and ATP7A via a microtubule‐stabilizing effect. Issue 11 (28th September 2021)

• Record Type: Journal Article
• Authors: Yu, Hang; Wang, Handong; Qie, Anran; Wang, Jiaqi; Liu, Yueping; Gu, Guoqiang; Yang, Jing; Zhang, Hanqiu; Pan, Wensen; Tian, Ziqiang; Wang, Chuan
• Is Part Of: Cancer science. Volume 112:Issue 11(2021)
• Page Start: 4655
• Page End: 4668
• Publication Date: 2021-09-28
• Subjects: ATP7A -- chemotherapy -- fibroblast growth factor 13 -- hCTR1 -- platinum drug; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.15137
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract: Platinum‐based regimens are the most widely used chemotherapy regimens, but cancer cells often develop resistance, which impedes therapy outcome for patients. Previous studies have shown that fibroblast growth factor 13 (FGF13) is associated with resistance to platinum drugs in HeLa cells. However, the mechanism and universality of this effect have not been clarified. Here, we found that FGF13 was associated with poor platinum‐based chemotherapy outcomes in a variety of cancers, such as lung, endometrial, and cervical cancers, through bioinformatics analysis. We then found that FGF13 simultaneously regulates the expression and distribution of hCTR1 and ATP7A in cancer cells, causes reduced platinum influx, and promotes platinum sequestration and efflux upon cisplatin exposure. We subsequently observed that FGF13‐mediated platinum resistance requires the microtubule‐stabilizing effect of FGF13. Only overexpression of FGF13 with the ‐SMIYRQQQ‐ tubulin‐binding domain could induce the platinum resistance effect. This phenomenon was also observed in SK‐MES‐1 cells, KLE cells, and 5637 cells. Our research reveals the mechanism of FGF13‐induced platinum drug resistance and suggests that FGF13 can be a sensibilization target and prognostic biomarker for chemotherapy. Abstract : Platinum drugs enter the cell via hCTR1 and are sequestered or expelled via ATP7A. Both hCTR1 degradation and ATP7A‐mediated drug sequestration or excretion are involved in vesicle transport. The microtubule‐stabilizing effect of FGF13 ensures these processes work properly.