Role of Glucose Metabolism Reprogramming in the Pathogenesis of Cholangiocarcinoma

Abstract

Cholangiocarcinoma (CCA) is one of the most lethal cancers, and its rate of occurrence is increasing annually. The diagnoses of CCA patients remain elusive due to the lack of early symptoms and is misdiagnosed as HCC in a considerable percentage of patients. It is crucial to explore the underlying mechanisms of CCA carcinogenesis and development to find out specific biomarkers for early diagnosis of CCA and new promising therapeutic targets. In recent times, the reprogramming of tumor cells metabolism has been recognized as a hallmark of cancer. The modification from the oxidative phosphorylation metabolic pathway to the glycolysis pathway in CCA meets the demands of cancer cell proliferation and provides a favorable environment for tumor development. The alteration of metabolic programming in cancer cells is complex and may occur via mutations and epigenetic modifications within oncogenes, tumor suppressor genes, signaling pathways, and glycolytic enzymes. Herein we review the altered metabolism in cancer and the signaling pathways involved in this phenomena as they may affect CCA development. Understanding the regulatory pathways of glucose metabolism such as Akt/mTOR, HIF1α, and cMyc in CCA may further develop our knowledge of this devastating disease and may offer relevant information in the exploration of new diagnostic biomarkers and targeted therapeutic approaches for CCA.

Dietary Copper Deficiency Leads to Changes in Gene Expression Indicating an Increased Demand for NADH in the Prefrontal Cortex of the Rat’s Brain

“…However, no increase in Ldha expression was found. On the other hand, it is known that c-myc is a transcription factor that directly activates the genes of the GLUT1 transporter and glycolytic enzymes, such as HK2, phosprofructokinase-1, and enolase-1 [ 51 ]. Furthermore, c-myc is an activator of Ldha expression [ 51 ].…”

Loss of FBP1 by aPKC-ι/Snail Pathway-Mediated Repression Promotes Invasion and Aerobic Glycolysis of Intrahepatic Cholangiocarcinoma

“…Glucose uptake is significantly enhanced in the cancer cells during EMT, which coincides with increased glycolysis (24,25) and lactate secretion that promote tumor invasion and distant metastasis (26,27). It is also reported that the reprogramming of tumor cell metabolism is a macroscopic change, and the change of ICC from oxidative phosphorylation to glycolysis provides favorable conditions for the proliferation of tumor cells (5)(6)(7).…”

“…It is the second most common primary liver tumor, and has poor prognosis (1) due to frequent metastasis and recalcitrance to radiotherapy and chemotherapy (2,3). Although notable improvements have been made with different preclinical available cholangiocarcinoma models (4)(5)(6), such as the fibroblast growth factor receptor 2 inhibitor pemigatinib, the first approval of a molecularly targeted treatment in patients with advanced cholangiocarcinoma by US Food and Drug Administration, the prognosis of this disease remains unsatisfactory (7). Therefore, further studies on the molecular mechanism of invasion and metastasis and exploring a novel and effective therapeutic target of ICC are urgently needed (8).…”

The Warburg effect promoted the activation of the NLRP3 inflammasome induced by Ni-refining fumes in BEAS-2B cells

“…Metabolic alteration is a typical hallmark of cancer cells (Chen et al, 2018). The process and the mechanism of cell carcinogenesis were very complex, but the most common and one of the first identified biochemical features of cancer cells was the Warburg effect (Pant et al, 2020). Therefore, we speculated that the inflammatory response may be related to the enhancement of the Warburg effect in normal cells.…”