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

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.