Tm4sf1, Transmembrane 4 L six family member 1, is a member of the L6 family and functions as a signal transducer. It is involved in regulating cell growth, tumor progression, and tissue differentiation, and is associated with pathways like Wnt/β -catenin [1,5]. Its abnormal expression is linked to various epithelial cancers, making it an important gene in cancer research [1-10].

Knockdown of Tm4sf1 in CRC cells inhibited migration, invasion, and tumour sphere formation, and suppressed the EMT mediated by TGF -β1. Mechanistically, it modulated SOX2 expression in a Wnt/β -catenin activation-dependent manner [1]. In ESCC cells, inhibiting FAK or knocking down Tm4sf1 attenuated cell migration and lung metastasis, as it promotes metastasis by interacting with integrin α6 [2]. In glioma cells, silencing Tm4sf1 inhibited proliferation, migration, invasion, induced cell cycle arrest and early apoptosis [3]. In HCC, knockdown of Tm4sf1 suppressed proliferation, induced non-secretory senescence, and enhanced the efficacy of anti-PD-1 therapy, as it regulated tumor cell senescence and immune evasion through the AKT pathway [4].

In conclusion, Tm4sf1 plays a significant role in promoting the malignancy of various cancers, including CRC, ESCC, glioma, and HCC. Loss-of-function experiments, such as gene knockdown in these cancer cell models, have revealed its key role in processes like EMT, metastasis, proliferation, and cell cycle regulation, providing potential therapeutic targets for these diseases.