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

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...

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Autores principales: Therachiyil, Lubna, Haroon, Javeria, Sahir, Fairooz, Siveen, Kodappully S., Uddin, Shahab, Kulinski, Michal, Buddenkotte, Joerg, Steinhoff, Martin, Krishnankutty, Roopesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Oncology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485421/
https://www.ncbi.nlm.nih.gov/pubmed/32984059
http://dx.doi.org/10.3389/fonc.2020.01744
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author Therachiyil, Lubna
Haroon, Javeria
Sahir, Fairooz
Siveen, Kodappully S.
Uddin, Shahab
Kulinski, Michal
Buddenkotte, Joerg
Steinhoff, Martin
Krishnankutty, Roopesh
author_facet Therachiyil, Lubna
Haroon, Javeria
Sahir, Fairooz
Siveen, Kodappully S.
Uddin, Shahab
Kulinski, Michal
Buddenkotte, Joerg
Steinhoff, Martin
Krishnankutty, Roopesh
author_sort Therachiyil, Lubna
collection PubMed
description 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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spelling pubmed-74854212020-09-24 Dysregulated Phosphorylation of p53, Autophagy and Stemness Attributes the Mutant p53 Harboring Colon Cancer Cells Impaired Sensitivity to Oxaliplatin Therachiyil, Lubna Haroon, Javeria Sahir, Fairooz Siveen, Kodappully S. Uddin, Shahab Kulinski, Michal Buddenkotte, Joerg Steinhoff, Martin Krishnankutty, Roopesh Front Oncol Oncology 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. Frontiers Media S.A. 2020-08-28 /pmc/articles/PMC7485421/ /pubmed/32984059 http://dx.doi.org/10.3389/fonc.2020.01744 Text en Copyright © 2020 Therachiyil, Haroon, Sahir, Siveen, Uddin, Kulinski, Buddenkotte, Steinhoff and Krishnankutty. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Therachiyil, Lubna
Haroon, Javeria
Sahir, Fairooz
Siveen, Kodappully S.
Uddin, Shahab
Kulinski, Michal
Buddenkotte, Joerg
Steinhoff, Martin
Krishnankutty, Roopesh
Dysregulated Phosphorylation of p53, Autophagy and Stemness Attributes the Mutant p53 Harboring Colon Cancer Cells Impaired Sensitivity to Oxaliplatin
title Dysregulated Phosphorylation of p53, Autophagy and Stemness Attributes the Mutant p53 Harboring Colon Cancer Cells Impaired Sensitivity to Oxaliplatin
title_full Dysregulated Phosphorylation of p53, Autophagy and Stemness Attributes the Mutant p53 Harboring Colon Cancer Cells Impaired Sensitivity to Oxaliplatin
title_fullStr Dysregulated Phosphorylation of p53, Autophagy and Stemness Attributes the Mutant p53 Harboring Colon Cancer Cells Impaired Sensitivity to Oxaliplatin
title_full_unstemmed Dysregulated Phosphorylation of p53, Autophagy and Stemness Attributes the Mutant p53 Harboring Colon Cancer Cells Impaired Sensitivity to Oxaliplatin
title_short Dysregulated Phosphorylation of p53, Autophagy and Stemness Attributes the Mutant p53 Harboring Colon Cancer Cells Impaired Sensitivity to Oxaliplatin
title_sort dysregulated phosphorylation of p53, autophagy and stemness attributes the mutant p53 harboring colon cancer cells impaired sensitivity to oxaliplatin
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485421/
https://www.ncbi.nlm.nih.gov/pubmed/32984059
http://dx.doi.org/10.3389/fonc.2020.01744
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