Frontiers in Oncology (Aug 2020)

Dysregulated Phosphorylation of p53, Autophagy and Stemness Attributes the Mutant p53 Harboring Colon Cancer Cells Impaired Sensitivity to Oxaliplatin

  • Lubna Therachiyil,
  • Lubna Therachiyil,
  • Javeria Haroon,
  • Fairooz Sahir,
  • Kodappully S. Siveen,
  • Shahab Uddin,
  • Shahab Uddin,
  • Michal Kulinski,
  • Joerg Buddenkotte,
  • Joerg Buddenkotte,
  • Martin Steinhoff,
  • Martin Steinhoff,
  • Martin Steinhoff,
  • Martin Steinhoff,
  • Martin Steinhoff,
  • Roopesh Krishnankutty

DOI
https://doi.org/10.3389/fonc.2020.01744
Journal volume & issue
Vol. 10

Abstract

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Colorectal cancer (CRC) forms one of the highest ranked cancer types in the world with its increasing incidence and mortality rates despite the advancement in cancer therapeutics. About 50% of human CRCs are reported to have defective p53 expression resultant of TP53 gene mutation often contributing to drug resistance. The current study was aimed to investigate the response of wild-type TP53 harboring HCT 116 and mutant TP53 harboring HT 29 colon cancer cells to chemotherapeutic drug oxaliplatin (OX) and to elucidate the underlying molecular mechanisms of sensitivity/resistance in correlation to their p53 status. OX inhibited growth of wild-type p53-harboring colon cancer cells via p53/p21-Bax mediated apoptosis. Our study revealed that dysregulated phosphorylation of p53, autophagy as well as cancer stemness attributes the mutant p53-harboring colon cancer cells impaired sensitivity to OX.

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