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Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor
07:16

Monitoring Hippo Signaling Pathway Activity Using a Luciferase-based Large Tumor Suppressor LATS Biosensor

Published on: September 13, 2018

20.4K

LATS1-Beclin1 mediates a non-canonical connection between the Hippo pathway and autophagy

Fengyuan Tang1, Gerhard Christofori1

  • 1Department of Biomedicine, University of Basel, Basel, Switzerland.

Molecular & Cellular Oncology
|September 18, 2020
PubMed

Insights

Large tumor suppressor 1 (LATS1) regulates sorafenib-induced autophagy in liver cancer, independent of kinase activity. This finding reveals a new mechanism in cancer therapy resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Biology

Background:

  • Therapy resistance is a major challenge in treating hepatocellular carcinoma (HCC).
  • Understanding evasive resistance mechanisms is crucial for developing effective cancer therapies.

Purpose of the Study:

  • To investigate the molecular mechanisms of sorafenib resistance in HCC.
  • To identify the role of LATS1 and LATS2 in regulating autophagy in HCC.

Main Methods:

  • Analysis of molecular mechanisms of therapy resistance in HCC.
  • Investigated the role of LATS1 and LATS2 in sorafenib-induced autophagy.
  • Examined LATS1's interaction with Beclin-1 (BECN1) ubiquitination and self-dimerization.

Main Results:

  • Discovered a kinase-activity independent role for LATS1, but not LATS2, in regulating sorafenib-induced lethal autophagy in HCC.
  • LATS1's autophagy regulatory role is general across various autophagy stimuli and depends on a specific LATS1 domain.
  • LATS1 regulates autophagy via BECN1 K27-linked ubiquitination and BECN1 self-dimerization.

Conclusions:

  • LATS1 plays a critical role in regulating autophagy and therapy response in HCC.
  • Highlights a novel, non-classical interaction between the Hippo signaling pathway and autophagy in cancer.
  • Provides potential therapeutic targets for overcoming sorafenib resistance in HCC.
Keywords:
K27-linkageUbiquitinationprotein stability

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