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Interaction between IGF2‐PI3K axis and cancer‐associated‐fibroblasts promotes anal squamous carcinogenesis
Author(s) -
Cacheux Wulfran,
Lièvre Astrid,
Richon Sophie,
Vacher Sophie,
El Alam Elsy,
Briaux Adrien,
El Botty Rania,
Mariani Pascale,
Buecher Bruno,
Schnitzler Anne,
Barbazan Jorge,
RomanRoman Sergio,
Bièche Ivan,
DanglesMarie Virginie
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32178
Subject(s) - pi3k/akt/mtor pathway , pten , carcinogenesis , cancer research , paracrine signalling , biology , cancer , protein kinase b , insulin like growth factor 1 receptor , growth factor , cancer associated fibroblasts , medicine , cancer cell , signal transduction , receptor , microbiology and biotechnology , genetics
Anal squamous cell carcinoma (ASCC) is a rare tumour, but its incidence is increasing. Standard chemoradiotherapy fails to cure 20% of patients and no targeted therapy is currently approved for recurrent ASCC. The PI3K/Akt/mTOR pathway is frequently altered in this poorly characterised carcinoma . IGF2 was identified here as a key factor in ASCC oncogenesis, as IGF2 was shown to play a crucial role in the PI3K pathway with frequent (~60%) and mutually exclusive genomic alterations in IGF2, IGF1R, PTEN and PIK3CA genes. We also demonstrated that IGF2 expression is mainly due to cancer‐associated fibroblasts and that IGF2 secreted by cancer‐associated fibroblasts from ASCC samples promotes proliferation of a human ASCC cell line via IGF2 paracrine signalling. Altogether, these results highlight the key role of the IGF2/PI3K axis, and the major role of cancer‐associated fibroblasts in tumour growth via IGF2 secretion, suggesting a major role of IGF2/IGF1R inhibitors in ASCC therapies.