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Genomic Hippo Pathway Alterations and Persistent YAP/TAZ Activation: New Hallmarks in Head and Neck Cancer

Farhoud Faraji1,2,3, Sydney I Ramirez3,4, Paola Y Anguiano Quiroz5

  • 1Department of Otolaryngology-Head and Neck Surgery, University of California San Diego Health, La Jolla, CA 92093, USA.

Cells
|April 23, 2022
PubMed

Insights

Head and neck squamous cell carcinoma (HNSCC) is a deadly cancer. Hippo pathway alterations, including FAT1, WWTR1, and YAP1 gene changes, drive HNSCC development and offer new therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Head and neck squamous cell carcinoma (HNSCC) remains a prevalent and lethal malignancy with limited therapeutic advancements.
  • Despite progress in surgery, radiation, and targeted treatments, prognosis for advanced HNSCC has stagnated, with poor response rates to immune checkpoint inhibitors.

Purpose of the Study:

  • To investigate the role of the Hippo signaling pathway in HNSCC development.
  • To identify specific genetic alterations within the Hippo pathway that contribute to HNSCC oncogenesis.
  • To explore potential therapeutic strategies targeting Hippo pathway vulnerabilities in HNSCC.

Main Methods:

  • Analysis of the human HNSCC oncogenome to identify genetic alterations.
  • Examination of mutations, deletions, and amplifications in key Hippo pathway genes (FAT1, WWTR1, YAP1).
  • Review of existing literature on Hippo pathway function and its role in cancer.

Main Results:

  • Genomic alterations impairing Hippo signaling and activating YAP/TAZ were identified in HNSCC.
  • FAT1 gene alterations (mutations/deletions) occurred in 29% of cases.
  • WWTR1 (TAZ) and YAP1 gene amplifications were observed in 14% and 8% of cases, respectively.

Conclusions:

  • Aberrant Hippo signaling, driven by genetic alterations in FAT1, WWTR1, and YAP1, is a significant oncogenic mechanism in HNSCC.
  • These findings highlight the Hippo pathway as a critical player in HNSCC initiation and progression.
  • Targeting Hippo pathway vulnerabilities presents a promising avenue for developing novel precision therapies for HNSCC.
Keywords:
FAT1HNSCHNSCCHippoTAZYAPhead and neck squamous cell carcinoma

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