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

Autor: Lubna Therachiyil, Javeria Haroon, Fairooz Sahir, Kodappully S. Siveen, Shahab Uddin, Michal Kulinski, Joerg Buddenkotte, Martin Steinhoff, Roopesh Krishnankutty
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Frontiers in Oncology, Vol 10 (2020)
Druh dokumentu: article
ISSN: 2234-943X
DOI: 10.3389/fonc.2020.01744
Popis: 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.
Databáze: Directory of Open Access Journals