Nuclear receptors, intestinal architecture and colon cancer: an intriguing link

Abstract

The intestinal epithelium is structured in crypt-villus units which are responsible for its continuous renewal. These units are organized in a dynamic scenario in which proliferating progenitor cells are generated from stem cells in the crypts and migrate along the villus axis until their extrusion as differentiated cells at the surface epithelium. The mechanisms controlling cell transition involve transcription factors that switch on and off compartment-specific genes. The Wnt cascade represents the dominant force controlling cell fate in the crypt-villus axis. Mutations in this cascade result in the development of colorectal cancer. Life-style modifications and dietary regimens are epidemiologically recognized contributing factors for intestinal tumorigenesis. Nuclear receptors are a family of transcription factors functioning as sensors of dietary and endogenous molecules, thus translating nutritional and hormonal stimuli into transcriptional modifications. This review presents the role of nuclear receptors in intestinal carcinogenesis and explores their influence in maintenance of intestinal epithelium architecture.

Efficacy of the Specific Endothelin A Receptor Antagonist Zibotentan (ZD4054) in Colorectal Cancer: A Preclinical Study

“…This may reflect trophic signaling roles for ET receptors along the basal to apical direction of cell turnover and differentiation. Similar functions have been postulated for retinoic acid receptors and vitamin D receptors, which are denser at the apex, and ERa found predominantly in basal regions (35). This pattern is consistent with ET B associated with growth arrest signaling and ET A associated with differentiation signaling.…”

Polymorphic CAG Repeat and Protein Expression of Androgen Receptor Gene in Colorectal Cancer

“…Steroid hormone receptors may participate in the differentiation, proliferation, and progression of colorectal cancer tissues (3,17,18). Many studies have focused on estrogen and progesterone, which were believed to have an important function in the development of colorectal cancer (19)(20)(21).…”

RIP140 increases APC expression and controls intestinal homeostasis and tumorigenesis

“…Indeed, several NRs exhibit a strongly deregulated expression in intestinal epithelium and have been shown to play an important physiopathological role in the intestine (34). For instance, receptors such as LRH-1 have promitotic activity, while others such as VDR, ER, and FxR play an antitumor role in mice (35). Some of these effects are mediated through regulation of the Wnt/APC/β-catenin signaling pathway by the corresponding NRs (36).…”