The role and mechanism of IFITM1 in developing acquired cisplatin resistance in small cell lung cancer

• DOI: 10.1016/j.heliyon.2024.e30806
• Publication Date: 2024-05-08T16:49:58Z
• Authors: Xuemei Wang; Haihong Qian; Ling Yang; Shuangli Yan; Hua Wang; Xiu Li; Donghai Yang
• Keywords: H1-99; 0301 basic medicine; 0303 health sciences; Science (General); Resistance; SCLC; IFITM1; Social sciences (General); Wnt; Q1-390; Cisplatin (CDDP); Research Article

Platinum-based chemotherapies, historically the cornerstone of first-line treatment for small-cell lung cancer (SCLC), face a major hurdle: frequent emergence chemoresistance, notably to cisplatin (CDDP). Current understanding mechanisms driving CDDP resistance in SCLC is incomplete. Notably, Interferon inducible transmembrane protein1 (IFITM1) has been identified as key player distant metastasis SCLC. Analysis The Cancer Genome Atlas (TCGA) database revealed that IFITM1 expression markedly elevated tumor tissues compared from adjacent normal tissues, correlating with worse prognosis patients Our research focused on investigating role acquisition Further clinical sample analysis highlighted significant increase levels cisplatin-resistant versus those were responsive CCDP treatment, similar trends observed cells. Crucially, overexpression reduced sensitivity cells cisplatin, while silencing enhanced chemosensitivity strains. vivo studies further confirmed significantly boosted efficacy inhibiting growth subcutaneous tumors NCI-H466/CDDP (cisplatin-resistant cells) mouse model. Mechanistically, appears foster through activation Wnt/β-catenin pathway. In summary, our findings suggest targeting IFITM1, alongside could offer promising therapeutic strategy overcome and improve outcomes patients.