Solute carrier family (SLC) amino acid transporters are upregulated in cutaneous squamous cell carcinoma

Solute carrier family (SLC) amino acid transporters play key role in maintaining a continuous supply of nutrients to cancer cells. Non melanoma skin tumours, the most common cancer type worldwide, undergo extensive metabolic rewiring to survive under hostile conditions. To adapt to nutrient-poor microenvironment, tumour cells often boost expression of the key metabolic enzymes. However, the role of the amino acid transporters and their therapeutic potential in non-melanoma skin cancer remain unclear. Here, we analyse publicly available transcriptomics data and identify several amino acid transporters that are strongly upregulated in skin cancer, including neutral amino acid transporter LAT1. LAT1 is overexpressed in proliferating basal-like cells within skin tumours and its level decreases during epidermal differentiation. Furthermore, we show that cutaneous squamous cell carcinoma cells rely on citrulline to survive under arginine scarcity and LAT1 is essential for citrulline import. Pharmacological inhibition of LAT1 by the small compound JPH203 sensitises cells to arginine deprivation. Altogether, we show that amino transporter LAT1 plays an important role in cutaneous squamous cell carcinoma growth in low arginine conditions and highlight its potential as a therapeutic target.