Epithelial-mesenchymal transition in cholangiocarcinoma: From clinical evidence to regulatory networks.
Cholangiocarcinoma (CCA) is an aggressive tumor with a poor prognosis due to its late clinical presentation and the lack of effective non-surgical therapies. Unfortunately, most of the patients are not eligible for curative surgery owing to the presence of metastases at the time of diagnosis. Therefore, it is important to understand the steps leading to cell dissemination in patients with CCA. To metastasize from the primary site, cancer cells must acquire migratory and invasive properties by a cell plasticity-promoting phenomenon known as epithelial-mesenchymal transition (EMT). EMT is a reversible dynamic process by which epithelial cells gradually adopt structural and functional characteristics of mesenchymal cells, and has lately become a centre of attention in the field of metastatic dissemination. In the present review, we aim to provide an extensive overview of the current clinical data and the prognostic value of different EMT markers that have been analysed in CCA. We summarize all the regulatory networks implicated in EMT from the membrane receptors to the main EMT-inducing transcription factors (SNAIL, TWIST and ZEB). Furthermore, since a tumor is a complex structure not exclusively formed by tumor cells, we also address the prominent role of the main cell types of the desmoplastic stroma that characterizes CCA in the regulation of EMT. Finally, we discuss the therapeutic considerations and difficulties faced to develop an effective anti-EMT treatment due to the redundancies and bypasses among the pathways regulating EMT.
INSERM, Sorbonne Universités, UPMC Univ Paris 06, Centre de Recherche Saint-Antoine (CRSA), F-75012 Paris, France; FONDATION ARC, F-94803 Villejuif, France.
Javier
J
Vaquero
Service d'Anatomie Pathologique Hôpital Beaujon, F-92110 Clichy, France; INSERM, UMR 1149, Centre de Recherche sur l'Inflammation, F-75018 Paris, France.
Nathalie
N
Guedj
INSERM, Sorbonne Universités, UPMC Univ Paris 06, Centre de Recherche Saint-Antoine (CRSA), F-75012 Paris, France.
Audrey
A
Clapéron
INSERM, Sorbonne Universités, UPMC Univ Paris 06, Centre de Recherche Saint-Antoine (CRSA), F-75012 Paris, France.
Thanh Huong
TH
Nguyen Ho-Bouldoires
Service d'Anatomie Pathologique Hôpital Beaujon, F-92110 Clichy, France; INSERM, UMR 1149, Centre de Recherche sur l'Inflammation, F-75018 Paris, France.
Valérie
V
Paradis
INSERM, Sorbonne Universités, UPMC Univ Paris 06, Centre de Recherche Saint-Antoine (CRSA), F-75012 Paris, France. Electronic address: laura.fouassier@inserm.fr.
Laura
L
Fouassier
D001650:Bile Duct Neoplasms / Q000175:diagnosis / Q000473:pathology; D018281:Cholangiocarcinoma / Q000175:diagnosis / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D006801:Humans; D011379:Prognosis
Chemoresistance; Cholangiocarcinoma; Epithelial-mesenchymal transition; Invasiveness; Tumor microenvironment