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The Hippo Tumor Suppressor Pathway (YAP/TAZ/TEAD/MST/LATS) and EGFR-RAS-RAF-MEK in cancer metastasis

Mohammad Reza Zinatizadeh1,2, Seyed Rouhollah Miri2, Peyman Kheirandish Zarandi1,2

  • 1Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Genes & Diseases
|February 11, 2021
PubMed

Insights

The Hippo pathway, crucial for organ size, is inactivated by RAS signaling. Loss of Hippo pathway function impacts cancer-driving RAS-RAF mutations and tumor progression.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Signal Transduction

Background:

  • The Hippo pathway is a critical regulator of organ size and tissue homeostasis by controlling cell proliferation and apoptosis.
  • It is activated by cell cycle arrest signals and inhibited by growth factors like EGF and LPA.
  • Key components include MST/LATS kinases and the YAP/TAZ transcriptional co-activators.

Purpose of the Study:

  • To elucidate the intricate relationship between the Hippo pathway and RAS signaling in the context of cancer.
  • To understand how dysregulation of the Hippo pathway influences the oncogenic activity of RAS-RAF mutations.

Main Methods:

  • Review of molecular mechanisms governing Hippo pathway activation and inactivation.
  • Analysis of the interplay between Hippo, TEAD transcription factors, and RAS-RAF signaling pathways.
  • Examination of the downstream consequences of Hippo pathway loss in cancer development.

Main Results:

  • The Hippo pathway, through YAP, regulates transcription factors (TEADs) involved in cell proliferation and stemness.
  • TEADs coordinate multiple signaling pathways, including Hippo, WNT, TGFβ, and EGFR.
  • RAS signaling is identified as a pivotal factor that inactivates the Hippo pathway, particularly through the EGFR-RAS-RAF-MEK-ERK cascade.

Conclusions:

  • Dysregulation of the Hippo pathway, especially its inactivation by RAS signaling, has profound implications for cancer.
  • The interplay between Hippo and RAS-RAF pathways highlights potential therapeutic targets in various cancers.
  • Understanding this crosstalk is essential for comprehending tumor progression, metastasis, and drug resistance.
Keywords:
CancerHippo pathwayMetastasisSignalingTumor suppressor

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