Thyroid Hormone Induces Oral Cancer Growth via the PD-L1-Dependent Signaling Pathway

Oral cancer is a fatal disease, and its incidence in Taiwan is increasing. Thyroid hormone as L-thyroxine (T-4) stimulates cancer cell proliferation via a receptor on integrin alpha v beta 3 of plasma membranes. It also induces the expression of programmed death-ligand 1 (PD-L1) and cell proliferation in cancer cells. Thyroid hormone also activates beta-catenin-dependent cell proliferation in cancer cells. However, the relationship between PD-L1 and cancer proliferation is not fully understood. In the current study, we investigated the role of inducible thyroid hormone-induced PD-L1-regulated gene expression and proliferation in oral cancer cells. Thyroxine bound to integrin alpha v beta 3 to induce PD-L1 expressions via activation of ERK1/2 and signal transducer and activator of transcription 3 (STAT3). Inactivated STAT3 inhibited PD-L1 expression and nuclear PD-L1 accumulation. Inhibition of PD-L1 expression reduced beta-catenin accumulation. Furthermore, nuclear PD-L1 formed a complex with nuclear proteins such as p300. Suppression PD-L1 expression by shRNA blocked not only expression of PD-L1 and beta-catenin but also signal transduction, proliferative gene expressions, and cancer cell growth. In summary, thyroxine via integrin alpha v beta 3 activated ERK1/2 and STAT3 to stimulate the PD-L1-dependent and beta-catenin-related growth in oral cancer cells.

Automated summary

This study found that thyroid hormone can activate ERK1/2 and STAT3 via integrin alpha v beta 3, promoting PD-L1-dependent and beta-catenin-related cell proliferation in oral cancer.