Regulation of metabolic reprogramming by tumor suppressor genes in pancreatic cancer

Abstract

Background: Pancreatic cancer continues to be one of the most aggressive malignant tumors. Work in recent years in cancer molecular biology has revealed that metabolic reprogramming is an additional hallmark of cancer that is involved in the pathogenesis of cancers, and is intricately linked to gene mutations. Main text: However, though oncogenes such as KRAS and c-Myc play important roles in the process, and have been extensively studied, no substantial improvements in the prognosis of pancreatic cancer have seen. Therefore, some scientists have tried to explain the mechanisms of abnormal cancer metabolism from the perspective of tumor suppressor genes. In this paper, we reviewed researches about how metabolic reprogramming was regulated by tumor suppressor genes in pancreatic cancer and their clinical implications. Conclusion: Abnormal metabolism and genetic mutations are mutually causal and complementary in tumor initiation and development. A clear understanding of how metabolic reprogramming is regulated by the mutated genes would provide important insights into the pathogenesis and ultimately treatment of pancreatic cancer.

Cellular metabolism in pancreatic cancer as a tool for prognosis and treatment (Review)

“…Other tumor suppressors frequently mutated in cancer cells have been linked to the altered cellular metabolism of various types of cancer, including PDAC ( 18 ). A homozygous deletion of the tumor suppressor gene locus SMAD4, which occurs in PDAC and can cause the loss of the malic enzyme 2 (ME2), was previously exploited to disrupt NADPH production, mitochondrial redox homeostasis and amino acid metabolism.…”

“…Alternative strategies to combat this lethal disease are therefore sought after and the targeting of the deregulated metabolic physiology, which is additionally connected to radio- and chemo-resistance in PDAC, is one of the promising options ( 16 , 17 ). The common genomic alterations, such as the activation of the KRAS oncogene, the deletion of the tumor suppressor gene, SMAD4, or the transformation of the tumor suppressor, p53, into a prooncogenic protein significantly stimulate nutrient acquisition and a variety of metabolic pathways ( 18 ). The ability to stratify PDAC tumors into subgroups with distinct metabolic requirements and vulnerabilities could offer valuable prognostic information and may aid to in the selection of specific treatments.…”

Metabolic profiles of regulatory T cells and their adaptations to the tumor microenvironment: implications for antitumor immunity

“…The expression of chemokine receptors, particularly chemokine (C–C motif) receptor 4 (CCR4), CCR7, CCR8, C–X–C chemokine receptor type 4 (CXCR4), and CXCR5 [ 19 , 20 ], contributes to the abundant accumulation of Tregs in the TME, where they are metabolically reprogrammed and functionally adapted to the low-nutrient, high-lactate environment. It is widely acknowledged that cellular metabolic reprogramming is a hallmark of cancer [ 1 , 21 ]. Furthermore, manipulation of cellular metabolism on the viability and function of both cancer cells and immune cells has aroused growing concern in the past decade, and considerable efforts have been made in checkpoint blockade immunotherapy and adoptive cellular treatment [ 22 , 23 ].…”

Studying the mechanism underlying lipid metabolism in osteosarcoma based on transcriptomic RNA sequencing and single‐cell data

“…A previous group 25 classified multiple tumors, such as ovarian cancer, 26 hepatocellular carcinoma, 27 and pancreatic cancer, 28,29 into different metabolic subgroups according to various metabolic pathways. Qian et al 15 identified two clusters and a three lipid metabolism‐related gene prognosis model for OS.…”