Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh, Sec-125, Noida-201313, (UP), India.
Anticancer Agents Med Chem. 2021;21(11):1369-1378. doi: 10.2174/1871520620666200721135230.
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.
头颈部鳞状细胞癌（HNSCC）是一种侵袭性恶性肿瘤，全球每年有超过 60 万例病例，预后不良，发病率高。HNSCC 肿瘤是发育不良的，多达 80%的成纤维细胞。据报道，癌相关成纤维细胞（CAFs）促进 HNSCC 的进展。与正常细胞不同，恶性细胞通常表现出增加的糖酵解，即使在有氧气的情况下；这一现象被称为沃伯格效应。因此，乳酸（LA）的产生增加。早些时候，据报道 HNSCC 肿瘤表现出高 LA 水平，与降低的存活率相关。据报道，CAF 分泌的肝细胞生长因子（HGF）激活受体酪氨酸激酶 c-MET，是 HNSCC 进展的主要促成事件。在鼻咽癌中，c-MET 抑制可下调 TP53 诱导的糖酵解和凋亡调节剂（TIGAR）和 NADPH 的产生，导致细胞凋亡。以前，已经证明 HNSCC 肿瘤细胞具有高度的糖酵解能力。此外，CAFs 显示出比 HNSCC 更高的利用 LA 作为碳源为线粒体呼吸供能的能力。早些时候，我们已经报道在混合培养中，两种细胞类型都增加了单羧酸转运蛋白（MCTs）的表达，以实现 LA 的双向转运。因此，MCTs 在头颈部癌症中癌细胞和癌症相关成纤维细胞之间的信号交叉对话中发挥重要作用，针对 MCTs 将导致头颈部癌症潜在治疗方法的发展。在这篇综述中，我们重点讨论了通过癌细胞和癌症相关成纤维细胞之间的信号交叉对话对头颈部癌症中 MCTs 的调节，针对这种信号交叉对话将导致头颈部癌症潜在治疗方法的发展。
