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

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

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.01744

DOI=10.3389/fonc.2020.01744

ISSN=2234-943X

ABSTRACT=<p>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 <italic>TP53</italic> gene mutation often contributing to drug resistance. The current study was aimed to investigate the response of wild-type <italic>TP53</italic> harboring HCT 116 and mutant <italic>TP53</italic> 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.</p>