Publication details
IFITM PROTEINS REGULATE SENSITIVITY OF CERVICAL CANCER CELLS TO CISPLATIN
| Authors | |
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| Year of publication | 2022 |
| Type | Conference abstract |
| Citation | |
| Description | Tumor therapy resistance is a frequent limiting factor to achieve cure of cancer patients. Therefore, an effort to elucidate mechanisms of this phenomenon is essential to make cancer treatment more effective. Upregulation of interferon-related DNA damage resistance signature (IRDS) genes was described in different radio- and chemotherapy resistant tumors. IRDS genes ensure prolonged viral and DNA damage resistance bringing tumors a selective advantage1. Interferon-induced transmembrane proteins (IFITMs), as a part of IRDS, provide cellular defense against broad range of viruses, while contributing to tumor progression. During our investigation focused on IFITM protein functions in tumors we described a linkage between these proteins and cellular response to chemotherapeutic drugs. Using cervical cancer cells, we proved enhanced cisplatin sensitivity of single IFITM1 or IFITM3 knock-out (KO) derivatives. Interestingly, double IFITM1/3 KO clones exert exclusive resistance to cisplatin. Therefore, we further investigate causes of the observed phenomenon. Using inductively coupled plasma mass spectrometry (ICP-MS) technique, we analyzed the cisplatin uptake and efflux rates revealing limited cisplatin influx by IFITM1/3 KO cells. Based on the differentially expressed proteins in IFITM1/3 KO cells after cisplatin treatment identified by pulse SILAC approach we focused our research also on the process of autophagy and vesicle trafficking. We continue to investigate the exact mechanism of IFITM proteins involvement in the chemoresistance of cancer cells. |