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

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...

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Autores principales: Baiocchi, Leonardo, Lenci, Ilaria, Milana, Martina, Kennedy, Lindsey, Sato, Keisaku, Zhang, Wenjun, Ekser, Burcin, Ceci, Ludovica, Meadows, Vik, Glaser, Shannon, Alpini, Gianfranco, Francis, Heather
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303798/
https://www.ncbi.nlm.nih.gov/pubmed/34359861
http://dx.doi.org/10.3390/cells10071692
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author Baiocchi, Leonardo
Lenci, Ilaria
Milana, Martina
Kennedy, Lindsey
Sato, Keisaku
Zhang, Wenjun
Ekser, Burcin
Ceci, Ludovica
Meadows, Vik
Glaser, Shannon
Alpini, Gianfranco
Francis, Heather
author_facet Baiocchi, Leonardo
Lenci, Ilaria
Milana, Martina
Kennedy, Lindsey
Sato, Keisaku
Zhang, Wenjun
Ekser, Burcin
Ceci, Ludovica
Meadows, Vik
Glaser, Shannon
Alpini, Gianfranco
Francis, Heather
author_sort Baiocchi, Leonardo
collection PubMed
description 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.
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spelling pubmed-83037982021-07-25 Cyclic AMP Signaling in Biliary Proliferation: A Possible Target for Cholangiocarcinoma Treatment? Baiocchi, Leonardo Lenci, Ilaria Milana, Martina Kennedy, Lindsey Sato, Keisaku Zhang, Wenjun Ekser, Burcin Ceci, Ludovica Meadows, Vik Glaser, Shannon Alpini, Gianfranco Francis, Heather Cells Review 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. MDPI 2021-07-04 /pmc/articles/PMC8303798/ /pubmed/34359861 http://dx.doi.org/10.3390/cells10071692 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Baiocchi, Leonardo
Lenci, Ilaria
Milana, Martina
Kennedy, Lindsey
Sato, Keisaku
Zhang, Wenjun
Ekser, Burcin
Ceci, Ludovica
Meadows, Vik
Glaser, Shannon
Alpini, Gianfranco
Francis, Heather
Cyclic AMP Signaling in Biliary Proliferation: A Possible Target for Cholangiocarcinoma Treatment?
title Cyclic AMP Signaling in Biliary Proliferation: A Possible Target for Cholangiocarcinoma Treatment?
title_full Cyclic AMP Signaling in Biliary Proliferation: A Possible Target for Cholangiocarcinoma Treatment?
title_fullStr Cyclic AMP Signaling in Biliary Proliferation: A Possible Target for Cholangiocarcinoma Treatment?
title_full_unstemmed Cyclic AMP Signaling in Biliary Proliferation: A Possible Target for Cholangiocarcinoma Treatment?
title_short Cyclic AMP Signaling in Biliary Proliferation: A Possible Target for Cholangiocarcinoma Treatment?
title_sort cyclic amp signaling in biliary proliferation: a possible target for cholangiocarcinoma treatment?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303798/
https://www.ncbi.nlm.nih.gov/pubmed/34359861
http://dx.doi.org/10.3390/cells10071692
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