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Updated: Aug 6, 2026
09:08
Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
Published on: January 12, 2020
ARID1A Stimulates Notch-TLL1 Signaling to Induce Cancer-Associated Fibroblast Activation and Intrahepatic
Sheng Xu1, Jing-Yi Huang2, Kang Wang3
1University of Chinese Academy of Sciences, Chinese Academy of Sciences Shanghai China.
Cancer Research
|July 17, 2026
Summary
ARID1A promotes intrahepatic cholangiocarcinoma (ICC) by sustaining Notch signaling and activating TLL1. This axis drives tumor progression, but acarbose inhibits TLL1, offering potential precision therapy for ICC.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Intrahepatic cholangiocarcinoma (ICC) is a deadly liver cancer with a dense desmoplastic stroma.
- The SWI/SNF complex component ARID1A is upregulated in ICC and contributes to its oncogenesis.
Purpose of the Study:
- To elucidate the oncogenic role of ARID1A in ICC.
- To identify downstream effectors and signaling pathways regulated by ARID1A.
- To explore potential therapeutic strategies targeting the ARID1A-driven pathway.
Main Methods:
- Investigated ARID1A expression and function in ICC models.
- Analyzed the impact of ARID1A on Notch signaling, autophagy, and lysosomal degradation.
- Identified TLL1 as a downstream effector and studied its role in activating hepatic stellate cells (HSCs).
- Utilized virtual screening to identify TLL1 inhibitors and tested acarbose efficacy in preclinical models.
Main Results:
- ARID1A stabilizes NICD1 by inhibiting AMPK-dependent autophagy, thereby enhancing Notch signaling.
- TLL1, a downstream effector, promotes ICC progression by activating HSCs.
- Ablation of TLL1 reduces cancer-associated fibroblast infiltration, collagen accumulation, and tumor growth.
- Acarbose effectively inhibits TLL1, suppressing HSC activation, collagen deposition, and tumor development in ICC models.
Conclusions:
- A tumor-promoting ARID1A/Notch/TLL1 axis drives ICC progression.
- TLL1 activation of HSCs is crucial for desmoplasia and tumor growth.
- Acarbose demonstrates potential as a precision therapy for ARID1A-high ICC patients by targeting the TLL1 pathway.
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