- 作者: Yu-Chen S. H. Yang, Po-Jui Ko, Yi-Shin Pan, Hung-Yun Lin, Jacqueline Whang-Peng, Paul J. Davis and Kuan Wang
- 作者服務機構: 1. Joint Biobank, Office of Human Research, Taipei Medical University, Taipei, 11031, Taiwan 2. School of Medicine, I-Shou University, Kaohsiung, 84001, Taiwan 3. Department of Pediatrics, E-DA Hospital, Kaohsiung, 82445, Taiwan 4. Graduate Institute of Nanomedicine and Medical Engineering, College of Medical Engineering, Taipei Medical University, Taipei, 11031, Taiwan 5. Graduate Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, 11031, Taiwan 6. Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei, 11031, Taiwan 7. Traditional Herbal Medicine Research Center of Taipei Medical University Hospital, Taipei Medical University, Taipei, 11031, Taiwan 8. TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, 11031, Taiwan 9. Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, 12144, USA 10. Albany Medical College, Albany, NY, 12144, USA
- 中文摘要:
- 英文摘要:
Thyroid hormone analogues—particularly, L-thyroxine (T4) has been shown to be relevant to the functions of a variety of cancers. Integrin αvβ3 is a plasma membrane structural protein linked to signal transduction pathways that are critical to cancer cell proliferation and metastasis. Thyroid hormones, T4 and to a less extend T3 bind cell surface integrin αvβ3, to stimulate the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway to stimulate cancer cell growth. Thyroid hormone analogues also engage in crosstalk with the epidermal growth factor receptor (EGFR)-Ras pathway. EGFR signal generation and, downstream, transduction of Ras/Raf pathway signals contribute importantly to tumor cell progression. Mutated Ras oncogenes contribute to chemoresistance in colorectal carcinoma (CRC); chemoresistance may depend in part on the activity of ERK1/2 pathway. In this review, we evaluate the contribution of thyroxine interacting with integrin αvβ3 and crosstalking with EGFR/Ras signaling pathway non-genomically in CRC proliferation. Tetraiodothyroacetic acid (tetrac), the deaminated analogue of T4, and its nano-derivative, NDAT, have anticancer functions, with effectiveness against CRC and other tumors. In Ras-mutant CRC cells, tetrac derivatives may overcome chemoresistance to other drugs via actions initiated at integrin αvβ3 and involving, downstream, the EGFR-Ras signaling pathways. - 中文關鍵字:
- 英文關鍵字: NDAT, Colorectal Cancer, Integrin αvβ3, Epidermal growth factor receptor, Ras mutation