Cisplatin Exposure of Squamous Cell Carcinoma Cells Leads to Modulation of the Autophagic Pathway

Rafael Guerrero-Preston, Edward A. Ratovitski

Research output: Chapter in Book/Report/Conference proceedingChapter

4 Scopus citations

Abstract

Platinum chemotherapy is beneficial for human epithelial cancers because the platinum agents induce DNA damage signaling, leading to initiation of cell cycle arrest and apoptosis, and ultimately to tumor cell death. However, tumor cells often develop chemoresistance to platinum anticancer drugs, because of the initiation of autophagic pathways serving as a cell-protective mechanism against these chemical stresses. Although the molecular events underlying these events are not yet completely understood, the critical role of tumor protein (TP)-p53 family members, as key players in guarding the genome and proteome integrity under stress, is very much appreciated. As transcriptional factors, TP53 members exert their functions through the transcriptional regulation of genes encoding the autophagic intermediates, while also affecting the transcription of microRNA by inducing or reducing their expression in tumor cells sensitive or resistant to chemotherapeutic anticancer drugs. These microRNAs subsequently modulate the expression of autophagic proteins and are very likely to change the molecular landscape of tumor-cell response to the anticancer drugs. Thus, a clear and in-depth understanding of molecular pathways leading to modulation of autophagic intermediates through transcription, microRNA modulation, and protein-protein interactions would lead to potentially beneficial adjustments of existing chemotherapeutics supplemented with small molecule- or microRNA-based regimens.

Original languageEnglish (US)
Title of host publicationMolecular Mechanisms
PublisherElsevier Inc.
Pages251-267
Number of pages17
Volume1
ISBN (Electronic)9780124055353
ISBN (Print)9780124055308
DOIs
StatePublished - 2014

Keywords

  • Autophagic signaling
  • Chemoresistance
  • Cisplatin
  • Platinum chemotherapy
  • Tumor protein (TP)-p53

ASJC Scopus subject areas

  • General Medicine
  • General Immunology and Microbiology

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