Phosphorylation and Stabilization of PIN1 by JNK Promote Intrahepatic Cholangiocarcinoma Growth

• Published in: Hepatology (Baltimore, Md.) Vol. 74; no. 5; pp. 2561 - 2579
• Main Authors: Lepore, Alessio, Choy, Pui Man, Lee, Nathan C.W., Carella, Maria Annunziata, Favicchio, Rosy, Briones‐Orta, Marco A., Glaser, Shannon S., Alpini, Gianfranco, D’Santos, Clive, Tooze, Reuben M., Lorger, Mihaela, Syn, Wing‐Kin, Papakyriakou, Athanasios, Giamas, Georgios, Bubici, Concetta, Papa, Salvatore
• Format: Journal Article
• Language: English
• Published: United States Wolters Kluwer Health, Inc 01.11.2021
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Bile Duct Neoplasms - drug therapy; Bile Duct Neoplasms - genetics; Bile Duct Neoplasms - metabolism; Bile Duct Neoplasms - pathology; Carcinogenesis - drug effects; Carcinogenesis - genetics; Carcinogenesis - metabolism; Cell Line, Tumor; Cell proliferation; Cholangiocarcinoma; Cholangiocarcinoma - drug therapy; Cholangiocarcinoma - genetics; Cholangiocarcinoma - metabolism; Cholangiocarcinoma - pathology; Female; Gene Knockdown Techniques; Hepatology; Humans; JNK protein; Kinases; Liver cancer; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - genetics; Mice; Mice, Inbred NOD; Mice, SCID; Mitogen-Activated Protein Kinase 8 - genetics; Mitogen-Activated Protein Kinase 8 - metabolism; Mitogen-Activated Protein Kinase 9 - genetics; Mitogen-Activated Protein Kinase 9 - metabolism; NIMA-Interacting Peptidylprolyl Isomerase - antagonists & inhibitors; NIMA-Interacting Peptidylprolyl Isomerase - genetics; NIMA-Interacting Peptidylprolyl Isomerase - metabolism; Phosphorylation; Phosphorylation - drug effects; Phosphorylation - genetics; Pin1 protein; Proteasomes; Retinoic acid; RNA, Small Interfering - genetics; Therapeutic targets; Tretinoin - administration & dosage; Tumor Burden - drug effects; Tumor Burden - genetics; Tumorigenesis; Ubiquitination; Xenograft Model Antitumor Assays; Xenografts

Background and Aims Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive type of liver cancer in urgent need of treatment options. Aberrant activation of the c‐Jun N‐terminal kinase (JNK) pathway is a key feature in ICC and an attractive candidate target for its treatment. However, the mecha...