Title:Targeting Signalling Cross-Talk between Cancer Cells and Cancer-Associated Fibroblast through Monocarboxylate Transporters in Head and Neck Cancer
Volume: 21
Issue: 11
Author(s): Vaishali Chandel and Dhruv Kumar*
Affiliation:
- Amity Institute of Molecular Medicine & Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh, Sec-125, Noida-201313, (UP),India
Keywords:
Head and neck cancer, Cancer-Associated Fibroblasts (CAFs), Monocarboxylate Transporters (MCTs), lactic acid, metabolism,
c-MET (Mesenchymal Epithelial Transition) factor, Hepatocyte Growth Factor (HGF).
Abstract: 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.
