IGFBP2 modulates the chemoresistant phenotype in esophageal adenocarcinoma

Oncotarget
Amy L MyersAndrew C Chang

Abstract

Esophageal adenocarcinoma (EAC) patients commonly present with advanced stage disease and demonstrate resistance to therapy, with response rates below 40%. Understanding the molecular mechanisms of resistance is crucial for improvement of clinical outcomes. IGFBP2 is a member of the IGFBP family of proteins that has been reported to modulate both IGF and integrin signaling and is a mediator of cell growth, invasion and resistance in other tumor types. In this study, high IGFBP2 expression was observed in a subset of primary EACs and was found to be significantly higher in patients with shorter disease-free intervals as well as in treatment-resistant EACs as compared to chemonaive EACs. Modulation of IGFBP2 expression in EAC cell lines promoted cell proliferation, migration and invasion, implicating a role in the metastatic potential of these cells. Additionally, knockdown of IGFBP2 sensitized EAC cells to cisplatin in a serum-dependent manner. Further in vitro exploration into this chemosensitization implicated both the AKT and ERK pathways. Silencing of IGFBP2 enhanced IGF1-induced immediate activation of AKT and reduced cisplatin-induced ERK activation. Addition of MEK1/2 (selumetinib or trametinib) or AKT (AKT Inhibitor VIII...Continue Reading

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Citations

Jan 11, 2019·Journal of Experimental & Clinical Cancer Research : CR·Zhangjian ZhouDunfa Peng
Mar 7, 2021·Biomolecules·Caterina MancarellaKatia Scotlandi

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Methods Mentioned

BETA
PCR
biopsies
transfection
light microscopy

Clinical Trials Mentioned

NCT01322802
NCT00821964
NCT02450097
NCT00503685
NCT01293032

Software Mentioned

SPOT Basic
Bioconductor
Affymetrix

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