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<sub>4</sub>) 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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2022-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/19/3050 |
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| author | Kuan-Wei Su Hung-Yun Lin Hsien-Chung Chiu Shin-Yu Shen Chun A. ChangOu Dana R. Crawford Yu-Chen S. H. Yang Ya-Jung Shih Zi-Lin Li Haw-Ming Huang Jaqueline Whang-Peng Yih Ho Kuan Wang |
| author_facet | Kuan-Wei Su Hung-Yun Lin Hsien-Chung Chiu Shin-Yu Shen Chun A. ChangOu Dana R. Crawford Yu-Chen S. H. Yang Ya-Jung Shih Zi-Lin Li Haw-Ming Huang Jaqueline Whang-Peng Yih Ho Kuan Wang |
| author_sort | Kuan-Wei Su |
| collection | DOAJ |
| description | Oral cancer is a fatal disease, and its incidence in Taiwan is increasing. Thyroid hormone as L-thyroxine (T<sub>4</sub>) 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. |
| first_indexed | 2024-03-09T21:54:08Z |
| format | Article |
| id | doaj.art-c64f343599974917a6dd74258222602d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T21:54:08Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-c64f343599974917a6dd74258222602d2023-11-23T20:01:48ZengMDPI AGCells2073-44092022-09-011119305010.3390/cells11193050Thyroid Hormone Induces Oral Cancer Growth via the PD-L1-Dependent Signaling PathwayKuan-Wei Su0Hung-Yun Lin1Hsien-Chung Chiu2Shin-Yu Shen3Chun A. ChangOu4Dana R. Crawford5Yu-Chen S. H. Yang6Ya-Jung Shih7Zi-Lin Li8Haw-Ming Huang9Jaqueline Whang-Peng10Yih Ho11Kuan Wang12Department of Dentistry, Hsinchu MacKay Memorial Hospital, Hsinchu City 30071, TaiwanGraduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanDepartment of Periodontology, School of Dentistry, National Defense Medical Center and Tri-Service General Hospital, Taipei 11490, TaiwanGraduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanCore Facility, Taipei Medical University, Taipei 11031, TaiwanDepartment of Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USAJoint Biobank, Office of Human Research, Taipei Medical University, Taipei 11031, TaiwanGraduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanGraduate Institute of Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, TaiwanSchool of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 11031, TaiwanCancer Center, Wan Fang Hospital, Taipei Medical University, Taipei 11031, TaiwanSchool of Pharmacy, Taipei Medical University, Taipei 11031, TaiwanGraduate Institute of Nanomedicine and Medical Engineering, College of Medical Engineering, Taipei Medical University, Taipei 11031, TaiwanOral cancer is a fatal disease, and its incidence in Taiwan is increasing. Thyroid hormone as L-thyroxine (T<sub>4</sub>) 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.https://www.mdpi.com/2073-4409/11/19/3050thyroxineoral cancerPD-L1β-catenin |
| spellingShingle | Kuan-Wei Su Hung-Yun Lin Hsien-Chung Chiu Shin-Yu Shen Chun A. ChangOu Dana R. Crawford Yu-Chen S. H. Yang Ya-Jung Shih Zi-Lin Li Haw-Ming Huang Jaqueline Whang-Peng Yih Ho Kuan Wang Thyroid Hormone Induces Oral Cancer Growth via the PD-L1-Dependent Signaling Pathway Cells thyroxine oral cancer PD-L1 β-catenin |
| title | Thyroid Hormone Induces Oral Cancer Growth via the PD-L1-Dependent Signaling Pathway |
| title_full | Thyroid Hormone Induces Oral Cancer Growth via the PD-L1-Dependent Signaling Pathway |
| title_fullStr | Thyroid Hormone Induces Oral Cancer Growth via the PD-L1-Dependent Signaling Pathway |
| title_full_unstemmed | Thyroid Hormone Induces Oral Cancer Growth via the PD-L1-Dependent Signaling Pathway |
| title_short | Thyroid Hormone Induces Oral Cancer Growth via the PD-L1-Dependent Signaling Pathway |
| title_sort | thyroid hormone induces oral cancer growth via the pd l1 dependent signaling pathway |
| topic | thyroxine oral cancer PD-L1 β-catenin |
| url | https://www.mdpi.com/2073-4409/11/19/3050 |
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