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

Yu Chen S.H. Yang, Po Jui Ko, Yi Shin Pan, Hung Yun Lin, Jacqueline Whang-Peng, Paul J. Davis, Kuan Wang

研究成果: 雜誌貢獻回顧型文獻同行評審

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.
原文英語
文章編號24
期刊Journal of Biomedical Science
28
發行號1
DOIs
出版狀態已發佈 - 十二月 2021

ASJC Scopus subject areas

  • 內分泌學、糖尿病和代謝
  • 分子生物學
  • 臨床生物化學
  • 細胞生物學
  • 生物化學(醫學)
  • 藥學(醫學)

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