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

Kuan Wei Su, Hung Yun Lin, Hsien Chung Chiu, Shin Yu Shen, Ou-Chun Chang, Dana R. Crawford, Yu-Chen Yang, Ya Jung Shih, Zi Lin Li, Haw Ming Huang, Jaqueline Whang-Peng, Yih Ho, Kuan Wang

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number3050
JournalCells
Volume11
Issue number19
DOIs
Publication statusPublished - Oct 2022

Keywords

  • oral cancer
  • PD-L1
  • thyroxine
  • β-catenin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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