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Updated: Sep 16, 2025

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LATS1/2-Integrin Axis Confers Tumor-Generated Forces That Activate Neighboring Fibroblasts.

Yanliang Liu1, Saisai Liu1, Yasuhisa Sakamoto1

  • 1Department of Molecular and Medical Pharmacology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.

Cancer Science
|July 7, 2025
PubMed
Summary
This summary is machine-generated.

Cancer cells generate forces essential for tumor growth by activating fibroblasts. The Hippo pathway kinases LATS1/2 regulate these forces, offering new therapeutic targets in cancer mechanobiology.

Keywords:
cancer‐associated fibroblasthippo pathwayintegrinsmechanobiologytumor microenvironment

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Area of Science:

  • Mechanobiology
  • Cancer Biology
  • Tumor Microenvironment

Background:

  • Tumors generate forces influencing progression, with fibroblasts traditionally seen as primary generators.
  • Recent evidence highlights cancer cells as significant contributors to tumor mechanical forces.
  • The regulatory pathways and roles of cancer cell-generated forces are not well understood.

Purpose of the Study:

  • To investigate the role of cancer cell-intrinsic pathways in generating mechanical forces within the tumor microenvironment.
  • To elucidate the mechanisms by which cancer cells contribute to force generation and influence surrounding cells.
  • To identify potential therapeutic targets based on the mechanobiology of tumor progression.

Main Methods:

  • Utilized murine breast cancer 4T1 spheroids to study force generation.
  • Investigated the function of Hippo pathway kinases LATS1/2 in cancer cells.
  • Analyzed extracellular matrix reorganization and fibroblast activation.
  • Examined the expression of collagen receptor integrins.

Main Results:

  • Deletion of LATS1/2 in cancer cells reduced collective force generation and disrupted collagen matrix.
  • LATS1/2-mediated forces are crucial for activating and differentiating fibroblasts into mechanoresponsive cells.
  • LATS1/2 regulate tumor force generation by modulating collagen receptor integrin expression.

Conclusions:

  • The Hippo pathway, specifically LATS1/2 in cancer cells, is essential for collective force generation and fibroblast activation.
  • Tumor-generated mechanical forces regulated by LATS1/2 are critical for fibroblast activation and differentiation.
  • Targeting the Hippo pathway offers a potential mechanobiological strategy for cancer therapy.