Increased expression of LAT1 in basal cell carcinoma: implications for tumour cell survival

Abstract

Summary Background Basal cell carcinoma (BCC) is the most common type of cancer in fair‐skinned individuals worldwide. Altered metabolism is a hallmark of cancer, and a growing body of evidence has shown increased expression of the large neutral amino acid transporter small subunit 1 (LAT1) in several types of cancers, including BCC. However, the mechanisms behind changed LAT1 expression in BCC are largely unknown. Aim To describe the protein expression of LAT1 and its colocalization with LAT2, and to examine LAT1 in association with BCC tumour biology characteristics such as cell proliferation, apoptosis and hypoxia. Methods Immunofluorescence stains were used on formalin‐fixed, paraffin‐embedded tissue samples (n = 14) from excised BCCs, and their protein‐staining patterns were examined. Results There was no correlation between expression of LAT1 and LAT2, and the colocalization was low. Compared with normal epidermis, there was significantly higher expression in BCC tissue of the proliferation markers topoisomerase IIα (P < 0.01) and Ki‐67 (P = 0.01). The fraction of LAT1‐expressing cells in BCC tissue was significantly (P < 0.01) inversely correlated with the fraction of proliferative active tumour cells. Cleaved caspase‐3 was significantly (P = 0.02) increased in tumour areas with high LAT1 expression. Conclusions The present study shows that LAT1 is not usually expressed by proliferating BCC cells. The morphological localization suggests that tumour cells use LAT1 to adapt to environmental changes such as starvation and/or hypoxia. These findings could have implications for future development of LAT1‐inhibitory BCC treatments.

A Prognostic Model for Colon Adenocarcinoma Patients Based on Ten Amino Acid Metabolism Related Genes

“…Apart from the well-known Warburg effect, metabolic alterations in lipid and amino acid metabolism have been observed in a number of tumors, including colorectal cancer, lung cancer, and breast cancer ( 7 ). Mounting evidence have indicated that changes in amino acid metabolism contributed to the metastasis, proliferation, angiogenesis, and drug resistance of colorectal cancer ( 8 – 11 ). Recent study has demonstrated that inhibition of ASCT2 (function as a glutamine transporter) exerted a great anti-tumor effect in colorectal cancer ( 12 ).…”

Construction and validation of a prognostic model for colon adenocarcinoma based on bile acid metabolism-related genes

“…The extent of cancer activity can be demonstrated by changes in cellular metabolic activity 21 . For example, the upregulation of glycolytic metabolism suggests exacerbation of COAD 22 , 23 while altered amino acid metabolism indicates metastasis, proliferation and drug resistance 24 – 26 . Normal bile acid metabolism contributes to the absorption of lipids, cholesterol and fat-soluble vitamins in the body and regulates the homeostasis of the epithelial environment of the gastrointestinal tract 27 .…”