CADM1 inhibits squamous cell carcinoma progression by reducing STAT3 activity.
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Volume
6
Pagination
24006 - ?
Publisher
DOI
10.1038/srep24006
Journal
Scientific Reports
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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.
Authors
Vallath, S; Sage, EK; Kolluri, KK; Lourenco, SN; Teixeira, VS; Chimalapati, S; George, PJ; Janes, SM; Giangreco, ACollections
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