Therapy resistance is a characteristic of cancer cells that significantly reduces the effectiveness of drugs. Despite the popularity of cisplatin (CP) as a chemotherapeutic agent, which is widely used in the treatment of various types of cancer, resistance of cancer cells to CP chemotherapy has been extensively observed. Among various reported mechanism(s), the epithelial–mesenchymal transition (EMT) process can significantly contribute to chemoresistance by converting the motionless epithelial cells into mobile mesenchymal cells and altering cell–cell adhesion as well as the cellular extracellular matrix, leading to invasion of tumor cells. By analyzing the impact of the different molecular pathways such as microRNAs, long non-coding RNAs, nuclear factor-κB (NF-ĸB), phosphoinositide 3-kinase-related protein kinase (PI3K)/Akt, mammalian target rapamycin (mTOR), and Wnt, which play an important role in resistance exhibited to CP therapy, we first give an introduction about the EMT mechanism and its role in drug resistance. We then focus specifically on the molecular pathways involved in drug resistance and the pharmacological strategies that can be used to mitigate this resistance. Overall, we highlight the various targeted signaling pathways that could be considered in future studies to pave the way for the inhibition of EMT-mediated resistance displayed by tumor cells in response to CP exposure.

https://www.mdpi.com/1422-0067/21/11/4002/pdf

Association of the Epithelial-Mesenchymal Transition (EMT) with Cisplatin Resistance.

Betulinic acid suppresses breast cancer aerobic glycolysis via caveolin-1/NF-κB/c-Myc pathway.

Purpose/Aim: Cancer cells are addicted to glycolytic anaerobic pathways, in presence or in absence of a functional Krebs' cycle (phenomenon Warburg). This metabolic predilection relies on both extr...

Expression of enzymes related to glucose metabolism in non-small cell lung cancer and prognosis.

Hypoxia-induced miR-214 expression promotes tumour cell proliferation and migration by enhancing the Warburg effect in gastric carcinoma cells.

Targeting pyruvate dehydrogenase kinase signaling in the development of effective cancer therapy.

Tumor cells prefer glycolysis (Warburg effect) during the proliferation and metastasis. The precise mechanism remains largely unknown. Here, we demonstrated that pyruvate dehydrogenase kinase 1 (PDK1) was a critical enzyme that functioned as an oncogene to promote non-small cell lung cancer (NSCLC) growth and metastasis. We discovered that PDK1 expression was significantly upregulated in NSCLC tissues and correlated with advanced T stage. Moreover, high expression of PDK1 was an independent prognostic factor of NSCLC. Ectopic overexpression of PDK1 promoted cell proliferation and inhibited apoptosis. Also it was shown that PDK1 increased the cell mobility when Transwell assay was performed. Further experiments indicated that PDK1 had a central role in metabolic reprogramming by phosphorylating pyruvate dehydrogenase, leading to enhanced Warburg effect. Collectively, our data reveal a new function for PDK1, which could be used to indicate the prognosis of NSCLC, and provide targeted therapeutic strategy for clinical treatment.

https://www.spandidos-publications.com/10.3892/or.2016.5253/download

Honglei Yin

Papers

PDK1 promotes tumor cell proliferation and migration by enhancing the Warburg effect in non-small cell lung cancer.