Abstract
Cholangiocytes, like most cells, express primary cilia extending from their membranes. These organelles function as antennae which detect stimuli from bile and transmit the information into cells regulating several signaling pathways involved in secretion, proliferation and apoptosis. The ability of primary cilia to detect different signals is provided by ciliary associated proteins which are expressed in its membrane. Defects in the structure and/or function of these organelles lead to cholangiociliopathies that result in cholangiocyte hyperproliferation, altered fluid secretion and absorption. Since primary cilia dysfunction has been observed in several epithelial tumors, including cholangiocarcinoma (CCA), primary cilia have been proposed as tumor suppressor organelles. In addition, the loss of cilia is associated with dysregulation of several molecular pathways resulting in CCA development and progression. Thus, restoration of the primary cilia may be a potential therapeutic approach for several ciliopathies and CCA.
Copyright © 2017 Elsevier B.V. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Absorption, Physiological / physiology
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Apoptosis / drug effects
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Apoptosis / physiology
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Bile Duct Neoplasms / drug therapy
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Bile Duct Neoplasms / etiology*
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Bile Duct Neoplasms / pathology
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Bile Ducts / cytology
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Bile Ducts / drug effects
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Bile Ducts / physiology*
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Cholangiocarcinoma / drug therapy
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Cholangiocarcinoma / etiology*
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Cholangiocarcinoma / pathology
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Cilia / drug effects
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Cilia / physiology
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Ciliopathies / drug therapy
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Ciliopathies / etiology*
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Ciliopathies / pathology
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Epithelial Cells / cytology
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Epithelial Cells / drug effects
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Epithelial Cells / physiology*
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Histone Deacetylase 6 / antagonists & inhibitors
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Histone Deacetylase 6 / metabolism
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Histone Deacetylase Inhibitors / pharmacology
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Histone Deacetylase Inhibitors / therapeutic use
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Humans
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Signal Transduction / drug effects
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Signal Transduction / physiology
Substances
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Antineoplastic Agents
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Histone Deacetylase Inhibitors
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HDAC6 protein, human
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Histone Deacetylase 6