Keratin 6, induced by chronic cisplatin exposure, confers chemoresistance in human gastric carcinoma cells.

Keratin 6, induced by chronic cisplatin exposure, confers chemoresistance in human gastric carcinoma cells. Oncol Rep. 2019 Jun 18;: Authors: Lim SC, Parajuli KR, Han SI Abstract Currently, various types of keratins have been reported to be highly expressed in cancer cells and to be associated with a malignant phenotype. In the present study, it was found that expression levels of keratin 6 (K6), keratin 16 (K16), and keratin 17 (K17) were highly elevated in SNU601 cells resistant to cisplatin (SNU601‑cis2 and SNU601‑cis10), but not in the parental SNU601 cells as confirmed by quantitative PCR, immunoblotting, and immunofluorescence assays. K6 is a type II keratin and is known to form a keratin filament in conjugation with type I keratin, K16 or K17. Thus, we attempted to understand the role of the overexpression of K6/K16 or K6/K17 keratin filaments by regulating the expression of K6. Silencing of K6 by siRNA in SNU601‑cis2 cells promoted oxaliplatin‑induced apoptosis in the resistant cells as shown by increased apoptotic body formation, caspase‑8 and caspase‑3 cleavage, and cytochrome c release. In addition, induction of K6 levels in wild‑type SNU601 cells, by transfection with pCMV6‑K6A and pCMV6‑K6B overexpression vectors, resulted in decreased apoptosis in response to cisplatin and L‑OHP. Platinum drugs, such as oxaliplatin, were shown to induce the extrinsic apoptotic pathway by inducing lipid raft formation...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research