論文 - 詳細
| RRC ID | 86963 |
|---|---|
| 著者 | Wulandari FS, Wang CY, Crawford DR, Yang YN, Then CK, Kumar S, Suk FM, Huang LY, Yang YS, Li ZL, Shih YJ, Tu HT, Wang K, Phu HD, Lin CM, Xuan DTM, Solomon DD, Lin HY, Whang-Peng J. |
| タイトル | Integrin αvβ3 is a Potential Therapeutic Target in Cholangiocarcinoma. |
| ジャーナル | Int J Med Sci |
| Abstract |
Cell surface receptors play vital roles in cancer growth and metastasis. Integrin αvβ3 is overexpressed in various cancer cells and interacts with different growth factors to stimulate cancer progression. Thyroid hormone binds to αvβ3 to activate signal transduction and cell proliferation. However, thyroxine (T4) deaminated analogue, tetraiodothyronine (tetrac), competes for the binding on integrin and inhibits cancer cell growth and metastasis. The current study investigated the pathogenic role of integrin αvβ3 and the potential of a novel therapeutic strategy targeted to integrin αvβ3. Pathogenetic studies of clinical samples revealed integrin αvβ3 cross-talked with EGFR and downstream signal transduction networks affected by thyroid hormone and EGF related to the progression of cholangiocarcinoma malignancy. Thyroxine and EGF stimulated PD-Ligand 1 (PD-L1) expression and cancer growth in cholangiocarcinoma. The thyroxine-induced PD-L1 accumulated in the nuclei and colocalized with p300. Alternatively, EGF increased cytosolic PD-L1 and nuclear accumulation of β-catenin. Targeting integrin αvβ3 with lipo-tetrac and its Dox-derivative induced anti-proliferation in vitro and in the xenografted animal model. Our research provides a fundamental understanding of the therapeutic role of integrin αvβ3 and the potential therapeutic approach in cholangiocarcinoma treatment. |
| 巻・号 | 23(3) |
| ページ | 889-915 |
| 公開日 | 2026-1-1 |
| DOI | 10.7150/ijms.125066 |
| PII | ijmsv23p0889 |
| PMID | 41799774 |
| PMC | PMC12964564 |
| MeSH | Animals Bile Duct Neoplasms* / drug therapy Bile Duct Neoplasms* / genetics Bile Duct Neoplasms* / pathology Cell Line, Tumor Cell Proliferation / drug effects Cholangiocarcinoma* / drug therapy Cholangiocarcinoma* / genetics Cholangiocarcinoma* / pathology Epidermal Growth Factor / metabolism ErbB Receptors / metabolism Gene Expression Regulation, Neoplastic / drug effects Humans Integrin alphaVbeta3* / antagonists & inhibitors Integrin alphaVbeta3* / genetics Integrin alphaVbeta3* / metabolism Mice Molecular Targeted Therapy Signal Transduction / drug effects Thyroxine* / analogs & derivatives Thyroxine* / pharmacology Thyroxine* / therapeutic use Xenograft Model Antitumor Assays |
| IF | 2.523 |
| リソース情報 | |
| ヒト・動物細胞 | SSP-25(RCB1293) HuCCT1(RCB1960) |