Notch signalling pathway in development of cholangiocarcinoma

Rauff, Bisma; Malik, Arif; Bhatti, Yasir Ali; Chudhary, Shafiq Ahmad; Qadri, Ishtiaq; Rafiq, Shafquat

doi:10.4251/wjgo.v12.i9.957

Cited by 13 publications

(15 citation statements)

References 104 publications

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“…Notch overactivation can result in liver epithelial cell dysplasia and malignant transformation. Indeed, Notch and Hes1 have been implicated in the development of cholangiocarcinoma, and inhibition of the signaling is a potential therapeutic target for the disease 19–21 . This study confirmed that cholangiocarcinoma developing in CD also exhibited nuclear overexpression of Notch1 and Hes1 in the cells.…”

Section: Discussionsupporting

confidence: 75%

Notch‐Hes1 signaling activation in Caroli disease and polycystic liver disease

Takahashi

Sato

Yamamura

et al. 2021

Pathology International

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The Notch signaling pathway plays a key role in the morphogenesis of the biliary tree, but its involvement in cystic biliary diseases, such as Caroli disease (CD) and polycystic liver disease (PLD), has yet to be determined. Immunostaining was performed using liver sections of CD and PLD, and the results were compared with those of congenital hepatic fibrosis (CHF) and von Meyenburg complex (VMC). The expression of Notch receptor 1 (Notch1) was increased in the nuclei of biliary epithelial cells in all cases of CD and PLD, whereas it remained at a low level in CHF and VMC. In addition, Notch2 and Notch3 were preferably expressed in the nuclei of biliary epithelial cells of PLD. Accordingly, the Notch effector Hes1 was highly expressed in biliary epithelial cells of CD and PLD, and the cell proliferative activity was significantly higher in CD and PLD. The expression of the Notch ligand Delta‐like 1 was significantly increased in biliary epithelial cells of CD and PLD, which may be causally associated with the nuclear overexpression of Notch1 and Hes1. These results indicate that aberrant activation of the Notch‐Hes1 signaling pathway may be responsible for the progression of biliary cystogenesis in CD and PLD.

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Section: Discussionsupporting

confidence: 75%

Notch‐Hes1 signaling activation in Caroli disease and polycystic liver disease

Takahashi

Sato

Yamamura

et al. 2021

Pathology International

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“…In the liver, hepatoblasts are the precursors of hepatocytes and cholangiocytes. Notch signaling can inhibit the differentiation of hepatoblasts into hepatocytes, allowing cholangiocyte formation [ 22 , 23 ]. Both the loss and gain of Notch functions may contribute to liver cancer development including both cholangiocarcinoma (CC) and HCC and different Notch receptors have different functions during liver cancer development [ 24 ].…”

Section: Notch Genesmentioning

confidence: 99%

Notch Signaling Regulation in HCC: From Hepatitis Virus to Non-Coding RNAs

Giovannini

Fornari

Piscaglia

et al. 2021

Cells

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The Notch family includes evolutionary conserved genes that encode for single-pass transmembrane receptors involved in stem cell maintenance, development and cell fate determination of many cell lineages. Upon activation by different ligands, and depending on the cell type, Notch signaling plays pleomorphic roles in hepatocellular carcinoma (HCC) affecting neoplastic growth, invasion capability and stem like properties. A specific knowledge of the deregulated expression of each Notch receptor and ligand, coupled with resultant phenotypic changes, is still lacking in HCC. Therefore, while interfering with Notch signaling might represent a promising therapeutic approach, the complexity of Notch/ligands interactions and the variable consequences of their modulations raises concerns when performed in undefined molecular background. The gamma-secretase inhibitors (GSIs), representing the most utilized approach for Notch inhibition in clinical trials, are characterized by important adverse effects due to the non-specific nature of GSIs themselves and to the lack of molecular criteria guiding patient selection. In this review, we briefly summarize the mechanisms involved in Notch pathway activation in HCC supporting the development of alternatives to the γ-secretase pan-inhibitor for HCC therapy.

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“…15,16 The Notch pathway plays a vital role in cholangiocyte differentiation, bile duct development, 17,18 and cholangiocarcinogenesis. 19,20 The overexpression of Notch receptors and ligands, such as Jagged1, has been reported in human iCCA. 19,20 Moreover, using genomic data from a vast iCCA collection, a recent study identified a Notch1 signature in human iCCA, suggesting the use of g-secretase inhibitors to treat this subgroup of patients.…”

mentioning

confidence: 99%

“…19,20 The overexpression of Notch receptors and ligands, such as Jagged1, has been reported in human iCCA. 19,20 Moreover, using genomic data from a vast iCCA collection, a recent study identified a Notch1 signature in human iCCA, suggesting the use of g-secretase inhibitors to treat this subgroup of patients. 21 The oncogenic role of the Notch pathway in iCCA has been investigated and validated in animal models.…”

mentioning

confidence: 99%