Lamc1 promotes the Warburg effect in hepatocellular carcinoma cells by regulating PKM2 expression through AKT pathway

Abstract

Hepatocellular carcinoma (HCC), the most common aggressive malignancy of liver, is the third leading cause of cancer death across the world. Laminin gamma 1 (Lamc1), encodes laminin-γ1, an extracellular matrix protein involved in various progresses such as tumor cell proliferation and metabolism. In the present study, high expression of Lamc1 and PKM2 was observed in tumor tissues of HCC patients. In vitro, down-regulation of Lamc1 inhibited proliferation of HCC cells by promoting cell death, reduced glucose consumption and lactate production, accompanied by a decrease in the expression of glucose transporter 1 (GLUT1) and lactate dehydrogenase A (LDHA), and PTEN increased, as well as PTEN S380 and AKT S473/T308 phosphorylation decreased, while Lamc1 up-regulation had the opposite effect. The effects of PKM2 were similar to that of Lamc1 and markedly counteracted the effects of Lamc1 down-regulation. In addition, Lamc1-induced increase in PKM2 expression was strongly attenuated by a PI3K inhibitor, LY294002 or a si-p110 PI3K, with a significant decrease in GLUT1 and LDHA expression, as well as decreased AKT T308 phosphorylation. Thus, we speculated that Lamc1 was implicated in the progression of HCC probably by regulating PKM2 expression through PTEN/AKT pathway.

Identification of a novel glycolysis-related gene signature for predicting metastasis and survival in patients with lung adenocarcinoma

“…Increased glycolysis, which is also called the “Warburg effect” [29, 30], has been found in several types of cancer and facilitates metastatic dissemination [31]. MiRNAs play an important role in the process of regulating glycolysis in cancer cells; for example, miR-143 can increase glucose metabolism and promote cell proliferation by targeting HK II directly in lung tumors [32].…”

A Novel Prognostic Index Based on the Analysis of Glycolysis-Related Genes in Head and Neck Squamous Cell Carcinomas

“…Compelling evidence has suggested that increased glycolysis is a hallmark of cancer cells [ 6 ]. Even under normal oxygen concentrations, the rate at which cancer cells metabolize glucose through glycolysis increases compared to normal cells [ 7 , 8 ]. This metabolic change increases glucose uptake and lactate production, thereby affecting cell growth, proliferation, angiogenesis, and invasion [ 5 , 9 , 10 ].…”

N-glycoproteomic Profiling Revealing New Coronavirus Therapeutic Targets That Maybe Involved in Cepharanthine’s Intervention

“…The protein (ITGA3) contains both up-and down-regulated glycosylation sites ( Figure 1D). LAMC1 was reported to be involved in cell proliferation, angiogenesis, growth, migration and invasion 11,12 . Remarkably, majority of the 9 aberrant glycoproteins in the key interaction module were enriched in ECM-receptor interaction pathways ( Figure 1D Coronavirus GX_P2V-induced alteration in protein glycosylation are prevalent in infected cells N-linked glycosylation was involved in multiple biological processes, such as receptor interactions, immune responses, protein secretion and transport, cell adhesion, signal transduction, etc.…”