Cyclic AMP Signaling in Biliary Proliferation: A Possible Target for Cholangiocarcinoma Treatment?

Cells

Shannon Glaser¹  Burcin Ekser²  Wenjun Zhang²  Ilaria Lenci³  Leonardo Baiocchi³  Martina Milana³  Keisaku Sato⁴  Gianfranco Alpini⁴  Vik Meadows⁴  Heather Francis⁴  Lindsey Kennedy⁴  Ludovica Ceci⁴ 

[1] Department of Medical Physiology, Texas A&M University College of Medicine, Bryan, TX 77807, USA;Division of Transplant Surgery, Department of Surgery, Indiana University, Indianapolis, IN 46202, USA;Hepatology Unit, University of Tor Vergata, 00133 Rome, Italy;Hepatology and Gastroenterology, Medicine, Indiana University, Indianapolis, IN 46202, USA;

关键词: cholangiocarcinoma;    cAMP;    cholangiocytes;    proliferation;    PKA;    secretin;   

DOI  :  10.3390/cells10071692

来源: DOAJ

【 摘 要 】

Cholangiocarcinoma is a lethal disease with scarce response to current systemic therapy. The rare occurrence and large heterogeneity of this cancer, together with poor knowledge of its molecular mechanisms, are elements contributing to the difficulties in finding an appropriate cure. Cholangiocytes (and their cellular precursors) are considered the liver component giving rise to cholangiocarcinoma. These cells respond to several hormones, neuropeptides and molecular stimuli employing the cAMP/PKA system for the translation of messages in the intracellular space. For instance, in physiological conditions, stimulation of the secretin receptor determines an increase of intracellular levels of cAMP, thus activating a series of molecular events, finally determining in bicarbonate-enriched choleresis. However, activation of the same receptor during cholangiocytes’ injury promotes cellular growth again, using cAMP as the second messenger. Since several scientific pieces of evidence link cAMP signaling system to cholangiocytes’ proliferation, the possible changes of this pathway during cancer growth also seem relevant. In this review, we summarize the current findings regarding the cAMP pathway and its role in biliary normal and neoplastic cell proliferation. Perspectives for targeting the cAMP machinery in cholangiocarcinoma therapy are also discussed.

【 授权许可】

Unknown