J Cancer 2019; 10(16):3819-3829. doi:10.7150/jca.30018

Research Paper

PGC1α downregulation and glycolytic phenotype in thyroid cancer

Chien-Liang Liu1,2, Po-Sheng Yang1, Tao-Yeuan Wang3, Shih-Yuan Huang1,2, Yi-Hue Kuo1,2, Shih-Ping Cheng1,4✉

1. Department of Surgery, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan
2. Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan
3. Department of Pathology, MacKay Memorial Hospital and Mackay Medical College, Taipei, Taiwan
4. Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

Abstract

Increased aerobic glycolysis portends an unfavorable prognosis in thyroid cancer. The metabolic reprogramming likely results from altered mitochondrial activity and may promote cancer progression. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) plays a pivotal role in mitochondrial biogenesis and function. In the present study, we aimed to evaluate the clinicopathological significance of PGC1α expression and the potential effects of PGC1α modulation. Firstly, the expression of PGC1α in thyroid cancer samples was evaluated using western blot analysis and immunohistochemical staining. Compared with normal thyroid tissue, PGC1α expression was downregulated in thyroid cancer. PGC1α-negative papillary cancer was associated with BRAF V600E mutation, large tumor size, extrathyroidal or lymphovascular invasion, lymph node metastasis, and advanced stage. The results were consistent with the analysis of The Cancer Genome Atlas data. PGC1α expression correlated with oxygen consumption in thyroid cancer cells and was inversely related to AKT activity. The biologic relevance of PGC1α was further investigated by gain- and loss-of-function experimental studies. PGC1α overexpression led to augmented oxidative metabolism and accelerated tumor growth, whereas PGC1α knockdown induced a glycolytic phenotype but reduced tumor growth in vivo. In conclusion, PGC1α downregulation is associated with glycolytic metabolism and advanced disease in thyroid cancer. Nonetheless, manipulating PGC1α expression and metabolic phenotype does not necessarily translate into beneficial effects. It suggests that the metabolic phenotype is likely the consequence rather than the cause of disease progression in thyroid cancer.

Keywords: PGC1α, Glycolysis, Thyroid cancer

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How to cite this article:
Liu CL, Yang PS, Wang TY, Huang SY, Kuo YH, Cheng SP. PGC1α downregulation and glycolytic phenotype in thyroid cancer. J Cancer 2019; 10(16):3819-3829. doi:10.7150/jca.30018. Available from http://www.jcancer.org/v10p3819.htm