Research Paper Volume 14, Issue 13 pp 5511—5522

Detachment stress mediated bioenergetic switch of malignant melanoma cells into anti-Warburg phenotype

WuChing Uen1,2, , TingTing Tseng1, , Ching-Po Wu1, , ShaoChen Lee1, ,

  • 1 School of Medicine, Fu Jen Catholic University, Xinzhuang, New Taipei City, Taiwan
  • 2 Department of Hematology and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Shih-Lin, Taipei City, Taiwan

Received: April 5, 2022       Accepted: June 27, 2022       Published: July 7, 2022      

https://doi.org/10.18632/aging.204164
How to Cite

Copyright: © 2022 Uen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

One of the biological features of cancer cells is their aerobic glycolysis by extensive glucose fermentation to harvest energy, so called Warburg effect. Melanoma is one of the most aggressive human cancers with poor prognosis and high mortality for its high metastatic ability. During the metastatic process, the metastatic tumor cells should survive under detachment stress. However, whether the detachment stress could affect the tumor phenotype is worthy to investigate.

We had established the cell model of human melanoma cells under detachment stress, which mimicked circulating melanoma. It had been demonstrated that the detachment stress altered melanoma cell activities, malignancy, and drug sensitivity. In this study, we found that adherent melanoma cells were more sensitive to glucose depletion. Gene expression profiling altered expressions of transporters associated with glucose metabolism. In addition, detachment stress reduced lactate secretion owing to the reduced MCT4 and GLUT1 expressions, the altered glycolytic and respiratory capacities, and the increased superoxide production. Detachment stress also increases the sensitivity of melanoma cells toward the blockade of electron transport chains. Investigation of the change in glucose metabolism of melanoma cells under detachment stress would be critical to provide a novel molecular mechanism to develop potential therapeutics.

Abbreviations

ECM: extracellular matrix; ECAR: extracellular acidification rate; 2DG: 2-deoxyglucose; OCR: oxygen consumption rate; ROS: reactive oxygen species; FCCP: p-trifluoromethoxyphenylhydrazone carbonyl cyanide.