TM4SF1 modulates the TGF-β1/Smad3 signaling pathway to affect malignant biological activity and autophagy of nasopharyngeal carcinoma cells

Abstract Objectives To explore whether transmembrane 4 superfamily 1 (TM4SF1) can modulate the transforming growth factor β1 (TGF-β1)/mothers against decapentaplegic homolog 3 (Smad3) signaling pathway to influence nasopharyngeal carcinoma (NPC) cells from the aspect of malignant biological activity and autophagy. Methods Reverse transcriptase-polymerase chain reaction was utilized for measuring the relative expression of TM4SF1 in human nasopharyngeal epithelial cell line (NP69) as well as human NPC cells (5–8F, CNE2, and 6–10B). A small interfering-negative control (si-NC) group, a si-TM4SF1 group, a si-TM4SF1 + TGF-β1 group, and a control group (not transfected with any plasmid) were established for the assignment of 5–8F cells in a random manner. Cell proliferation, apoptosis, autophagy, and protein expression were evaluated by Cell Counting Kit-8 assay, flow cytometry, monodansylcadaverine (MDC) staining/transmission electron microscopy (TEM), and Western blotting, respectively. Results We found that TM4SF1 expression was higher in human NPC 5–8F, CNE2, and 6–10B cells than in NP69 cells, and its relative expression significantly rose in 5–8F cells compared with 6–10B and CNE2 cells (p<0.05). In comparison to the si-TM4SF1 group, the cell viability, number of invaded cells, and relative expression of TM4SF1, p-Smad3/Smad3 ratio and protein expressions of p62, TGF-β1 and N-cadherin in cells were elevated in the si-TM4SF1 + TGF-β1 group, together with the reductions in apoptosis rate, relative fluorescence intensity, number of autophagosomes, and LC3-II/LC3-Ι ratio and protein expressions of Beclin1 and E-cadherin in cells (p<0.05). Conclusions TM4SF1 knockdown is able to influence NPC cells by repressing their proliferation and infiltration while inducing their apoptosis.