The Role of PGC-1α in Digestive System Malignant Tumours

Abstract

Background: Cancer is increasingly becoming the leading cause of death in many countries, and malignant tumours of the digestive system account for majority of cancer incidence and mortality cases. Metabolism has been identified as a core hallmark of cancer. Peroxisome proliferator activated receptor gamma coactivator-1 alpha (PGC-1α) is a pivotal regulator of mitochondrial energy metabolism. Accumulating evidence reveals that PGC-1α is essential in cancer development.

Objective: We summarize the latest research progress of PGC-1α in common digestive system malignant tumours. Some related modulators and pathways are analyzed as well.

Methods: We conducted a literature review on the development of PGC-1α in common digestive system malignant tumours.

Results: In colorectal cancer, PGC-1α appears to provide growth advantages by different pathways, although it has also been reported to have opposite effects. The previous studies of PGC-1α on liver cancer also demonstrated different effects by sundry pathways. Concerning gastric cancer, PGC-1α promotes cell proliferation, apoptosis in vitro and tumour growth in vivo. AMPK/SIRT1/PGC-1α is related to the inhibition of apoptosis in pancreatic cancer cells. Pancreatic cancer stem cells are strongly dependent on mitochondrial oxidative phosphorylation. PGC-1α is required to maintain the stemness property of pancreatic cancer stem cells.

Conclusion: We explore diverse mechanisms that explain the dichotomous functions of PGC-1α on tumorigenesis, and discuss the latest research concerning digestive system malignant tumours. This review would provide better comprehension of the field and a basis for further studies associated with PGC-1α in digestive system cancers.

Keywords: PGC-1α; cancer; colorectal cancer; digestive system; liver cancer; metabolism..