Snail Enhances Glycolysis in the Epithelial-Mesenchymal Transition Process by Targeting FBP1 in Gastric Cancer

Abstract

Background: Snail is a key regulator of epithelial-mesenchymal transition (EMT) in cancer. However, the regulatory role and underlying mechanisms of Snail in gastric cancer metabolism are unknown. In this study, we characterized the regulation of aerobic glycolysis by Snail in gastric cancer. Methods: The impact of Snail on glucose metabolism was studied in vitro. Combining maximum standardized uptake value (SUVmax), which was obtained preoperatively via a PET/CT scan, with immunohistochemistry staining, we further analyzed the correlation between SUVmax and Snail expression in gastric cancer tissues. Results: Increased expression of Snail promoted lactate production, glucose utilization, and decreased FBP1 expression at both mRNA and protein level. The expression level of Snail was positively associated with SUVmax in gastric cancer patients (P=0.022). Snail and FBP1 expression were inversely correlated at both mRNA and protein level (P=0.002 and P=0.015 respectively) in gastric cancer tissues. Further studies demonstrated that Snail inhibited the FBP1 gene expression at the transcriptional level. Restoring FBP1 expression reversed the effects of glycolysis and EMT induced by Snail in gastric cancer cells. Conclusions: Our results thus reveal that Snail serves as a positive regulator of glucose metabolism through regulation of the FBP1 in gastric cancer. Disrupting the Snail-FBP1 signaling axis may be effective to prevent primary tumor EMT and glycolysis process.

PGK1 is a Potential Survival Biomarker and Invasion Promoter by Regulating the HIF-1α–Mediated Epithelial-Mesenchymal Transition Process in Breast Cancer

“…As anticipated, knockdown of PGK1 expression significantly upregulated epithelial marker E-cadherin and downregulated mesenchymal markers N-cadherin and vimentin. Some studies have demonstrated that glycolytic enzymes are involved in the EMT process, including FBP1 [10,11,22], PKM2 [23], and LDHA. Glycolytic enzymes are also regulated by classic EMT regulators [11,[24][25][26], so, it is not surprising that PGK1 can regulate the EMT process in breast cancer.…”

Aldolase A as a prognostic factor and mediator of progression via inducing epithelial–mesenchymal transition in gastric cancer

“…Despite recent advancements in diagnosis and therapeutic methods, the prognosis of GC is still poor and the 5‐year survival rate for patients with GC has remained 20%‐25% . The survival of patients largely depends on the disease stage at diagnosis. The tumour–node–metastasis staging system has been widely used as an effective approach to predict the prognosis of and determine the treatment option for GC.…”

“…This phenomenon is named as the Warburg effect or aerobic glycolysis. The Warburg effect was considered to be at the root of carcinogenesis and progression . It not only provides cancer cells with adenosine triphosphate (ATP) and nutrients but also leads to an acidic environment that facilitates metastasis .…”

“…The Warburg effect was considered to be at the root of carcinogenesis and progression . It not only provides cancer cells with adenosine triphosphate (ATP) and nutrients but also leads to an acidic environment that facilitates metastasis . Glycolysis represents a 10‐step metabolic process that involves multiple enzymes .…”

AAED1 modulates proliferation and glycolysis in gastric cancer

“…Under acidic conditions, the extracellular matrix becomes unstable, which favors the metastasis of cancer cells (32,33). For example, in gastric cancer cells, epithelial-mesenchymal-transition (EMT) regulator Snail-mediated repression of glycolytic enzyme fructose-bisphosphatase 1 (FBP1) provides metastatic advantages to gastric cancer cells (34). Some EMT regulators such as Twist1, are also HIF1α targets.…”