Thyroid Hormone Nuclear Receptor TRα1 and Canonical WNT Pathway Cross-Regulation in Normal Intestine and Cancer

Abstract

A pivotal role of thyroid hormones and their nuclear receptors in intestinal development and homeostasis have been described, whereas their involvement in intestinal carcinogenesis is still controversial. In this perspective article we briefly summarize the recent advances in this field and present new data regarding their functional interaction with one of the most important signaling pathway, such as WNT, regulating intestinal development and carcinogenesis. These complex interactions unveil new concepts and will surely be of importance for translational research.

The relationship between thyroid and cancer (focus on breast cancer)

“…relationship between thyroid hormones and proliferation, apoptosis, invasion and angiogenesis of several types of cancer [3]. While αvβ3 receptors are thought to regulate most of the tumor-promoting effects of THs in breast cancer (BC) cells, TRs seem to have tumor-supressing properties in BC [8].…”

“…While αvβ3 receptors are thought to regulate most of the tumor-promoting effects of THs in breast cancer (BC) cells, TRs seem to have tumor-supressing properties in BC [8]. The αvβ3 receptor has two different sites of binding to hormones (S1 and S2), being that each one translates into different signaling cascades [3]. The S1 binds only to T3, leading to activation of the intracellular PI3K (phosphatidylinositol-3-kinase) signaling pathway, and induction of the expression of hypoxia-inducing factor 1 (HIF-1).…”

“…This activated pathway induces the fibroblast growth factor-2 (FGF-β), that stimulates angiogenesis and tumor growth. In this way, activation of the αvβ3 integrin receptor facilitates the proliferative action of thyroid hormones on neoplastic cells and stimulates angiogenesis [3]. The MAPK pathway also infuences estrogen receptors activity and localization.…”