TY - JOUR
T1 - Bile acids and colon cancer
T2 - Is FXR the solution of the conundrum?
AU - Gadaleta, Raffaella Maria
AU - Garcia-Irigoyen, Oihane
AU - Moschetta, Antonio
N1 - Funding Information:
A. Moschetta is funded by Italian Association for Cancer Research (AIRC, IG 18987), NR-NET FP7 Marie Curie ITN, Italian Ministry of University and Education (Finanziamenti per la Ricerca di Base IDEAS RBID08C9N7; PRIN 2010FHH32M-002), Italian Ministry of Health (Young Researchers Grant GR-2008-1143546; GR-2010-2314703), and University of Bari (IDEA GRBA0802SJ-2008).
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/8
Y1 - 2017/8
N2 - Diet and lifestyle habits have a profound impact on the pathophysiology of many diseases. Colorectal cancer (CRC) is the third most common cancer worldwide and its etiology is strongly influenced by nutrition and high fat/high carbohydrate Western-style diet. Human epidemiological and animal studies have shown that colonic cancer risk is also related to faecal bile acid concentration. Abnormally high levels of bile acids (BA) trigger the colonic mucosa with a plethora of detrimental effects such as DNA oxidative damage, inflammation and hyperproliferation that highly promote CRC progression in post-initiation phase. The Farnesoid X receptor (FXR) is a nuclear receptor that transcriptionally mediates the signalling activity of BAs. FXR regulates BA metabolism mainly maintaining BA concentrations within a physiological range, thereby preventing BA-induced cytotoxicity. In fact, loss of FXR is associated with higher BA concentrations and with a pro-tumorigenic phenotype. Here we explore the liaison connecting nutrition, intestinal epithelium renewal, BA and their nuclear receptor FXR in CRC. Moreover, we summarize evidence linking BA and CRC, as well as examine current understanding of the protumoral actions of BA and the bona fide antitumoral properties of FXR.
AB - Diet and lifestyle habits have a profound impact on the pathophysiology of many diseases. Colorectal cancer (CRC) is the third most common cancer worldwide and its etiology is strongly influenced by nutrition and high fat/high carbohydrate Western-style diet. Human epidemiological and animal studies have shown that colonic cancer risk is also related to faecal bile acid concentration. Abnormally high levels of bile acids (BA) trigger the colonic mucosa with a plethora of detrimental effects such as DNA oxidative damage, inflammation and hyperproliferation that highly promote CRC progression in post-initiation phase. The Farnesoid X receptor (FXR) is a nuclear receptor that transcriptionally mediates the signalling activity of BAs. FXR regulates BA metabolism mainly maintaining BA concentrations within a physiological range, thereby preventing BA-induced cytotoxicity. In fact, loss of FXR is associated with higher BA concentrations and with a pro-tumorigenic phenotype. Here we explore the liaison connecting nutrition, intestinal epithelium renewal, BA and their nuclear receptor FXR in CRC. Moreover, we summarize evidence linking BA and CRC, as well as examine current understanding of the protumoral actions of BA and the bona fide antitumoral properties of FXR.
KW - Bile acids
KW - Colorectal cancer
KW - Gene expression
KW - Gut-liver axis
KW - Nuclear receptors
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U2 - 10.1016/j.mam.2017.04.002
DO - 10.1016/j.mam.2017.04.002
M3 - Review article
C2 - 28400119
AN - SCOPUS:85018772276
SN - 0098-2997
VL - 56
SP - 66
EP - 74
JO - Molecular aspects of medicine
JF - Molecular aspects of medicine
ER -