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Updated: Dec 12, 2025

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
Published on: September 13, 2018
RNA-binding protein Musashi2 regulates Hippo signaling via SAV1 and MOB1 in pancreatic cancer
Haiyan Yang1,2, Jiong Hu1,2, Jingde Chen3
1Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Abstract:
Musashi 2 (MSI2), a member of the Musashi RNA-binding family, is reported to be an oncoprotein in pancreatic ductal adenocarcinoma (PDAC), but the mechanisms of MSI2 in the development and progression of PDAC have not been fully demonstrated. In this research, we studied the clinical significance, biologic effects and the underlying mechanism of MSI2 in the progression of PDAC. The expression of MSI2, Mps-binding protein 1 (MOB1) and Salvador family WW domain-containing protein 1 (SAV1) in PDAC tissues were analyzed immunohistochemically. The biologic effects of MSI2 regarding PDAC cell proliferation, migration and invasion were studied using gain- and loss-of-function assays. MSI2 regulated Hippo signaling pathway via SAV1 and MOB1 was tested in several PDAC cell lines, and the mechanisms were studied using molecular biologic methods. The expression of MSI2 was significantly increased in PDAC cell lines and tissues, and positively associated with tumor poorer differentiation, lymph nodes metastasis and TNM stages. Overexpression of MSI2 promoted PDAC cells proliferation, migration and invasion. Further studies demonstrated that MSI2 regulated the Hippo signaling pathway via directly binding to the mRNAs of SAV1 and MOB1, and controlled the translation and stability of SAV1 and the translation of MOB1. This study demonstrated that MSI2 regulated the Hippo signaling pathway via suppressing SAV1 and MOB1 at post-transcriptional level and promoted PDAC progression.
Insights
Musashi 2 (MSI2) promotes pancreatic cancer progression by suppressing SAV1 and MOB1. This oncoprotein disrupts the Hippo signaling pathway at a post-transcriptional level, driving tumor growth and metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Musashi 2 (MSI2) is implicated as an oncoprotein in pancreatic ductal adenocarcinoma (PDAC).
- The precise mechanisms by which MSI2 drives PDAC development and progression remain incompletely understood.
- Understanding MSI2's role is crucial for developing targeted therapies for PDAC.
Purpose of the Study:
- To investigate the clinical significance of MSI2 in PDAC.
- To elucidate the biological effects of MSI2 on PDAC cell behavior.
- To uncover the underlying molecular mechanisms of MSI2 in PDAC progression, focusing on the Hippo signaling pathway.
Main Methods:
- Immunohistochemical analysis of MSI2, MOB1, and SAV1 expression in PDAC tissues.
- Gain- and loss-of-function assays to assess MSI2's impact on PDAC cell proliferation, migration, and invasion.
- Molecular biology techniques to investigate MSI2's regulation of the Hippo signaling pathway via SAV1 and MOB1.
Main Results:
- MSI2 expression is significantly elevated in PDAC cell lines and tissues.
- Increased MSI2 correlates with poorer tumor differentiation, lymph node metastasis, and advanced TNM stages.
- MSI2 overexpression enhances PDAC cell proliferation, migration, and invasion.
Conclusions:
- MSI2 directly binds to SAV1 and MOB1 mRNAs, suppressing their translation and stability at the post-transcriptional level.
- MSI2 dysregulates the Hippo signaling pathway by inhibiting SAV1 and MOB1, thereby promoting PDAC progression.
- Targeting MSI2 may offer a therapeutic strategy for pancreatic cancer.
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