Role of thyroid hormone-integrin αvβ3-signal and therapeutic strategies in colorectal cancers

Journal of Biomedical Science

Jacqueline Whang-Peng¹  Hung-Yun Lin²  Kuan Wang³  Yi-Shin Pan³  Yu-Chen S. H. Yang⁴  Paul J. Davis⁵  Po-Jui Ko⁶ 

[1] Graduate Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, 11031, Taipei, Taiwan;Cancer Center, Wan Fang Hospital, Taipei Medical University, 11031, Taipei, Taiwan;Graduate Institute for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, 11031, Taipei, Taiwan;Cancer Center, Wan Fang Hospital, Taipei Medical University, 11031, Taipei, Taiwan;Traditional Herbal Medicine Research Center of Taipei Medical University Hospital, Taipei Medical University, 11031, Taipei, Taiwan;TMU Research Center of Cancer Translational Medicine, Taipei Medical University, 11031, Taipei, Taiwan;Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 12144, Albany, NY, USA;Graduate Institute of Nanomedicine and Medical Engineering, College of Medical Engineering, Taipei Medical University, 11031, Taipei, Taiwan;Joint Biobank, Office of Human Research, Taipei Medical University, 11031, Taipei, Taiwan;Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, 12144, Albany, NY, USA;Albany Medical College, 12144, Albany, NY, USA;School of Medicine, I-Shou University, 84001, Kaohsiung, Taiwan;Department of Pediatrics, E-DA Hospital, 82445, Kaohsiung, Taiwan;

关键词: NDAT;    Colorectal Cancer;    Integrin αvβ3;    Epidermal growth factor receptor;    Ras mutation;   

DOI  :  10.1186/s12929-021-00719-5

来源: Springer

【 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.

【 授权许可】

CC BY