Glucose metabolism changes during the development and progression of oral tongue squamous cell carcinomas

Abstract

Previous studies have revealed several genes involved in the carcinogenesis of oral cancer. However, the detailed mechanisms underlying this process are poorly understood. Previously, we established a database cataloging the transcriptional progression profile of oral carcinogenesis and identified several candidate genes with continuously increasing or decreasing expression, which specifically promote the transition of oral premalignant lesions to invasive carcinomas. In this study, using our microarray database, we attempted to determine significant genes that may contribute to metabolic alterations during oral carcinogenesis. After performing a literature survey, we focused on 15 candidate genes associated with glucose metabolism changes, particularly the tri-carboxylic acid cycle, and investigated the mRNA-expression status of these genes with our database. Only the solute carrier family 2 member 1 gene (also known as GLUT1), showed significantly increased mRNA expression during oral tumorigenesis. Immunohistochemical analysis confirmed that GLUT1 protein expression significantly increased during oral carcinogenesis. In addition, tumors with high expression of this protein significantly correlated with nodal status (P=0.002). Kaplan-Meier survival curves clearly demonstrated the adverse impact of high GLUT1 protein expression on disease-free survival (P=0.004). GLUT1 mRNA and protein expression increased in the order of normal mucosal tissues, epithelial dysplastic lesions and invasive carcinomas. Therefore, metabolic alterations, especially in glucose metabolism, occurred at the very early stage of development of oral malignancies. In addition, GLUT1 played a significant role in oral cancer, acquiring a malignant phenotype.

High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia

“…It has been demonstrated that glycolysis metabolism was associated with tumor cell development and progression in oral tongue squamous cell carcinomas (38). In the results of the present study, regardless of whether PD-L1 was overexpressed or knocked-down, the expression of HK2 and LDHA was increased or decreased in AML cells MOLM-13 with cell proliferation altered, which was consistent with the results observed in other tumor types (38). Several studies have reported the impact of glycolysis in AML.…”

“…Targeting HK2 with costunolide decreased the uptake of glucose and lactate accumulation, resulting in suppression of hepatic stellate cell viability, which is the major cell for hepatic fibrosis (37). It has been demonstrated that glycolysis metabolism was associated with tumor cell development and progression in oral tongue squamous cell carcinomas (38). In the results of the present study, regardless of whether PD-L1 was overexpressed or knocked-down, the expression of HK2 and LDHA was increased or decreased in AML cells MOLM-13 with cell proliferation altered, which was consistent with the results observed in other tumor types (38).…”

AZGP1 suppresses the process of colorectal cancer after upregulating FASN expression via mTOR signal pathway

“…At present, the malignant phenotype of most tumor tissues is closely related to the metabolisms of special material and energy, such as oral cancer (Nakazato et al 2019), hepatocellular carcinoma (Fang et al 2019), pancreatic cancer (Yang et al 2019), non-small cell lung cancer (Zhang et al 2019), prostate cancer (Marin de Mas et al 2019), etc. Colorectal cancer (CRC) is the most frequent malignant gastrointestinal tumor and a leading cause of cancer death worldwide, along with an increase of about 150,000 cases every year (Jemal et al 2008).…”

Aberrant GLUT1 Expression Is Associated With Carcinogenesis and Progression of Liver Fluke-associated Cholangiocarcinoma

“…In addition, high GLUT1 expression was found in the advanced non-papillary type and larger tumor sizes of CCA. The increasing expression of GLUT1 during progression of cancer may be an essential characteristic of cancer as this event was also observed in many types of cancer, such as cervical cancer (23), hepatoma (24), and oral tongue squamous cell carcinomas (25).…”