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Targeting Signalling Cross-Talk between Cancer Cells and Cancer-Associated Fibroblast through Monocarboxylate Transporters in Head and Neck Cancer

头颈部鳞状细胞癌 癌症 癌症研究 癌细胞 瓦博格效应 受体酪氨酸激酶 肿瘤微环境 厌氧糖酵解 癌相关成纤维细胞 医学 生物 细胞生物学 头颈部癌 激酶 内科学
作者
Vaishali Chandel,Dhruv Kumar
出处
期刊:Anti-cancer Agents in Medicinal Chemistry [Bentham Science Publishers]
卷期号:21 (11): 1369-1378 被引量:5
标识
DOI:10.2174/1871520620666200721135230
摘要

Head and Neck Squamous Cell Carcinoma (HNSCC) is an aggressive malignancy affecting more than 600,000 cases worldwide annually, associated with poor prognosis and significant morbidity. HNSCC tumors are dysplastic, with up to 80% fibroblasts. It has been reported that Cancer-Associated Fibroblasts (CAFs) facilitate HNSCC progression. Unlike normal cells, malignant cells often display increased glycolysis, even in the presence of oxygen; a phenomenon known as the Warburg effect. As a consequence, there is an increase in Lactic Acid (LA) production. Earlier, it has been reported that HNSCC tumors exhibit high LA levels that correlate with reduced survival. It has been reported that the activation of the receptor tyrosine kinase, c- MET, by CAF-secreted Hepatocyte Growth Factor (HGF) is a major contributing event in the progression of HNSCC. In nasopharyngeal carcinoma, c-MET inhibition downregulates the TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) and NADPH production resulting in apoptosis. Previously, it was demonstrated that HNSCC tumor cells are highly glycolytic. Further, CAFs show a higher capacity to utilize LA as a carbon source to fuel mitochondrial respiration than HNSCC. Earlier, we have reported that in admixed cultures, both cell types increase the expression of Monocarboxylate Transporters (MCTs) for a bidirectional LA transporter. Consequently, MCTs play an important role in signalling cross-talk between cancer cells and cancer associate fibroblast in head and neck cancer, and targeting MCTs would lead to the development of a potential therapeutic approach for head and neck cancer. In this review, we focus on the regulation of MCTs in head and neck cancer through signalling cross-talk between cancer cells and cancer-associated fibroblasts, and targeting this signalling cross talk would lead to the development of a potential therapeutic approach for head and neck cancer.
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