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Volume 10
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10.3390/cells10071692
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Review

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

by
Leonardo Baiocchi
1,
Ilaria Lenci
1,
Martina Milana
1,
Lindsey Kennedy
2,3,
Keisaku Sato
2,
Wenjun Zhang
4,
Burcin Ekser
4,
Ludovica Ceci
2,
Vik Meadows
2,
Shannon Glaser
5,
Gianfranco Alpini
2,3,*,† and
Heather Francis
2,3,*,†
1
Hepatology Unit, University of Tor Vergata, 00133 Rome, Italy
2
Hepatology and Gastroenterology, Medicine, Indiana University, Indianapolis, IN 46202, USA
3
Richard L. Roudebush VA Medical Center, Indianapolis, IN 46202, USA
4
Division of Transplant Surgery, Department of Surgery, Indiana University, Indianapolis, IN 46202, USA
5
Department of Medical Physiology, Texas A&M University College of Medicine, Bryan, TX 77807, USA
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2021, 10(7), 1692; https://doi.org/10.3390/cells10071692
Submission received: 25 May 2021 / Revised: 30 June 2021 / Accepted: 30 June 2021 / Published: 4 July 2021
(This article belongs to the Special Issue New Aspects and Mechanisms in Liver Diseases)
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Abstract

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.
Keywords: cholangiocarcinoma; cAMP; cholangiocytes; proliferation; PKA; secretin cholangiocarcinoma; cAMP; cholangiocytes; proliferation; PKA; secretin

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MDPI and ACS Style

Baiocchi, L.; Lenci, I.; Milana, M.; Kennedy, L.; Sato, K.; Zhang, W.; Ekser, B.; Ceci, L.; Meadows, V.; Glaser, S.; et al. Cyclic AMP Signaling in Biliary Proliferation: A Possible Target for Cholangiocarcinoma Treatment? Cells 2021, 10, 1692. https://doi.org/10.3390/cells10071692

AMA Style

Baiocchi L, Lenci I, Milana M, Kennedy L, Sato K, Zhang W, Ekser B, Ceci L, Meadows V, Glaser S, et al. Cyclic AMP Signaling in Biliary Proliferation: A Possible Target for Cholangiocarcinoma Treatment? Cells. 2021; 10(7):1692. https://doi.org/10.3390/cells10071692

Chicago/Turabian Style

Baiocchi, Leonardo, Ilaria Lenci, Martina Milana, Lindsey Kennedy, Keisaku Sato, Wenjun Zhang, Burcin Ekser, Ludovica Ceci, Vik Meadows, Shannon Glaser, and et al. 2021. "Cyclic AMP Signaling in Biliary Proliferation: A Possible Target for Cholangiocarcinoma Treatment?" Cells 10, no. 7: 1692. https://doi.org/10.3390/cells10071692

APA Style

Baiocchi, L., Lenci, I., Milana, M., Kennedy, L., Sato, K., Zhang, W., Ekser, B., Ceci, L., Meadows, V., Glaser, S., Alpini, G., & Francis, H. (2021). Cyclic AMP Signaling in Biliary Proliferation: A Possible Target for Cholangiocarcinoma Treatment? Cells, 10(7), 1692. https://doi.org/10.3390/cells10071692

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