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- Title
Thyroid Hormone Induces Oral Cancer Growth via the PD-L1-Dependent Signaling Pathway.
- Authors
Su, Kuan-Wei; Lin, Hung-Yun; Chiu, Hsien-Chung; Shen, Shin-Yu; ChangOu, Chun A.; Crawford, Dana R.; Yang, Yu-Chen S. H.; Shih, Ya-Jung; Li, Zi-Lin; Huang, Haw-Ming; Whang-Peng, Jaqueline; Ho, Yih; Wang, Kuan
- Abstract
Oral cancer is a fatal disease, and its incidence in Taiwan is increasing. Thyroid hormone as L-thyroxine (T4) stimulates cancer cell proliferation via a receptor on integrin αvβ3 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 β-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 αvβ3 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 β-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 β-catenin but also signal transduction, proliferative gene expressions, and cancer cell growth. In summary, thyroxine via integrin αvβ3 activated ERK1/2 and STAT3 to stimulate the PD-L1-dependent and β-catenin-related growth in oral cancer cells.
- Subjects
TAIWAN; PROGRAMMED cell death 1 receptors; ORAL cancer; TUMOR growth; PROGRAMMED death-ligand 1; THYROID hormones; CELLULAR signal transduction
- Publication
Cells (2073-4409), 2022, Vol 11, Issue 19, p3050
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells11193050