Slc7a5-flox Mouse

Slc7a5, also known as LAT1, is an amino acid transporter. It forms a heterodimeric complex with 4F2hc (SLC3A2), which is crucial for the efficient uptake of essential amino acids and hormones. This transporter promotes cellular growth by stimulating mTORC1 signaling and repressing the integrated stress response (ISR) [5].

Cancer cells rely on increased nutrient uptake, and Slc7a5 is highly expressed in various cancers, related to poor patient prognosis. Pharmacologic inhibition and knockdown/knockout of Slc7a5 suppress cancer cell proliferation and xenograft tumor growth. It inhibits protein synthesis by downregulating mTORC1 and mobilizing the GAAC pathway. In triple-negative breast cancer, knocking down Slc7a5 inhibited cell proliferation, migration, invasion, and increased CD8+ T-cell infiltration. The combination of a Slc7a5 blockade and anti-PD-1 antibody synergistically inhibited tumor progression [1,6]. In gastric cancer, circARID1A promotes cancer proliferation by forming a circARID1A-IGF2BP3-SLC7A5 RNA-protein ternary complex, increasing SLC7A5 mRNA stability [3]. In lung cancer, IGF2BP2 enhances SLC7A5 mRNA stability and translation through m6A modification, and this positive feedback loop promotes radioresistance [4].

In conclusion, Slc7a5 is essential for cellular growth through its role in amino acid transport and associated signaling pathways. Studies using knockout or knockdown models have revealed its significant contribution to cancer progression, highlighting its potential as a molecular target for cancer diagnosis and therapeutics. Additionally, it may play a role in enhancing anti-tumor immunity and is involved in the regulation of ferroptosis in head and neck squamous cell carcinoma [1,2,6,7].