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

  • Authors:
    • Sung‑Chul Lim
    • Keshab Raj Parajuli
    • Song Iy Han
  • View Affiliations

  • Published online on: June 18, 2019     https://doi.org/10.3892/or.2019.7201
  • Pages: 797-804
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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 and death receptor recruitment into lipid rafts. However, in the resistant cells, the oxaliplatin‑triggered extrinsic apoptotic pathway appeared to be suppressed by decreased lipid raft formation, and recruitment of death receptor 5 and FADD into lipid rafts. Therefore, the increase in the levels of the K6 filament may be associated with the regulation of lipid raft formation and may contribute, at least in part, to resistance to anticancer drugs.

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Copy and paste a formatted citation
APA
Lim, S., Parajuli, K.R., & Han, S.I. (2019). Keratin 6, induced by chronic cisplatin exposure, confers chemoresistance in human gastric carcinoma cells. Oncology Reports, 42, 797-804. https://doi.org/10.3892/or.2019.7201
MLA
Lim, S., Parajuli, K. R., Han, S. I."Keratin 6, induced by chronic cisplatin exposure, confers chemoresistance in human gastric carcinoma cells". Oncology Reports 42.2 (2019): 797-804.
Chicago
Lim, S., Parajuli, K. R., Han, S. I."Keratin 6, induced by chronic cisplatin exposure, confers chemoresistance in human gastric carcinoma cells". Oncology Reports 42, no. 2 (2019): 797-804. https://doi.org/10.3892/or.2019.7201