Oxidative Phosphorylation Promotes Primary Melanoma Invasion.

The American Journal of Pathology
Amel SalhiIman Osman

Abstract

Dermal invasion is a hallmark of malignant melanoma. Although the molecular alterations that drive the progression of primary melanoma to metastatic disease have been studied extensively, the early progression of noninvasive primary melanoma to an invasive state is poorly understood. To elucidate the mechanisms underlying the transition from radial to vertical growth, the first step in melanoma invasion, we developed a zebrafish melanoma model in which constitutive activation of ribosomal protein S6 kinase A1 drives tumor invasion. Transcriptomic analysis of ribosomal protein S6 kinase A1-activated tumors identified metabolic changes, including up-regulation of genes associated with oxidative phosphorylation. Vertical growth phase human melanoma cells show higher oxygen consumption and preferential utilization of glutamine compared to radial growth phase melanoma cells. Peroxisome proliferator activated receptor γ coactivator (PGC)-1α, has been proposed as a master regulator of tumor oxidative phosphorylation. In human primary melanoma specimens, PGC1α protein expression was found to be positively associated with increased tumor thickness and expression of the proliferative marker Ki-67 and the reactive oxygen species scavenger...Continue Reading

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Citations

May 28, 2020·Cells·William Tyler Frantz, Craig J Ceol
Nov 17, 2020·Frontiers in Immunology·Ya-Nan XueWei-Qiang Tan
Feb 8, 2021·Trends in Cell Biology·Aastha Garde, David R Sherwood
May 4, 2021·Frontiers in Oncology·Chandra K SinghNihal Ahmad

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