CADM1 inhibits squamous cell carcinoma progression by reducing STAT3 activity

Sabari Vallath, Elizabeth K Sage, Krishna K Kolluri, Sofia N Lourenco, Vitor S Teixeira, Suneeta Chimalapati, P Jeremy George, Sam M Janes, Adam Giangreco

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Although squamous cell carcinomas (SqCCs) of the lungs, head and neck, oesophagus, and cervix account for up to 30% of cancer deaths, the mechanisms that regulate disease progression remain incompletely understood. Here, we use gene transduction and human tumor xenograft assays to establish that the tumour suppressor Cell adhesion molecule 1 (CADM1) inhibits SqCC proliferation and invasion, processes fundamental to disease progression. We determine that the extracellular domain of CADM1 mediates these effects by forming a complex with HER2 and integrin α6β4 at the cell surface that disrupts downstream STAT3 activity. We subsequently show that treating CADM1 null tumours with the JAK/STAT inhibitor ruxolitinib mimics CADM1 gene restoration in preventing SqCC growth and metastases. Overall, this study identifies a novel mechanism by which CADM1 prevents SqCC progression and suggests that screening tumours for loss of CADM1 expression will help identify those patients most likely to benefit from JAK/STAT targeted chemotherapies.

Original languageEnglish
Article number24006
JournalScientific Reports
Volume6
DOIs
Publication statusPrint publication - 1 Apr 2016
Externally publishedYes

Keywords

  • Animals
  • Carcinoma, Squamous Cell/metabolism
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules/genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Female
  • Gene Expression Profiling
  • Humans
  • Immunoglobulins/genetics
  • Integrin alpha6beta4/metabolism
  • Lung Neoplasms/metabolism
  • Membrane Proteins/metabolism
  • Mice
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Nitriles
  • Pyrazoles/chemistry
  • Pyrimidines
  • Receptor, ErbB-2/genetics
  • STAT3 Transcription Factor/metabolism
  • Uterine Cervical Neoplasms/metabolism

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