Department of Molecular, Cell and Cancer Biology; Department of Pathology; Graduate School of Biomedical Sciences
Amino Acids, Peptides, and Proteins | Cancer Biology | Cells | Molecular Biology | Neoplasms | Oncology | Pathology | Respiratory Tract Diseases | Therapeutics
The insulin-like growth factor-1 (IGF-1) signaling pathway has been implicated in non-small cell lung cancer (NSCLC) outcomes and resistance to targeted therapies. However, little is known regarding the molecular mechanisms by which this pathway contributes to the biology of NSCLC. The insulin receptor substrate (IRS) proteins are cytoplasmic adaptor proteins that signal downstream of the IGF-1R and determine the functional outcomes of this signaling pathway. In this study, we assessed the expression patterns of IRS-1 and IRS-2 in NSCLC to identify associations between IRS-1 and IRS-2 expression levels and survival outcomes in the two major histological subtypes of NSCLC, adenocarcinoma (ADC) and squamous cell carcinoma (SCC). High IRS-2 expression was significantly associated with decreased overall survival in adenocarcinoma (ADC) patients, whereas low IRS-1 cytoplasmic expression showed a trend toward association with decreased overall survival in squamous cell carcinoma (SCC) patients. Tumors with low IRS-1 and high IRS-2 expression were found to be associated with poor outcomes in ADC and SCC, indicating a potential role for IRS-2 in the aggressive behavior of NSCLC. Our results suggest distinct contributions of IRS-1 and IRS-2 to the biology of ADC and SCC that impact disease progression.
Adenocarcinomas, Non-small cell lung cancer, Cytoplasmic staining, Squamous cell carcinomas, Nuclear staining, Membrane staining, Cell staining, Lung and intrathoracic tumors
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Copyright: © 2019 Piper et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
PLoS One. 2019 Aug 8;14(8):e0220567. doi: 10.1371/journal.pone.0220567. eCollection 2019. Link to article on publisher's site
Piper AJ, Clark JL, Mercado-Matos JR, Matthew-Onabanjo AN, Hsieh C, Akalin A, Shaw LM. (2019). Insulin Receptor Substrate-1 (IRS-1) and IRS-2 expression levels are associated with prognosis in non-small cell lung cancer (NSCLC). Open Access Articles. https://doi.org/10.1371/journal.pone.0220567. Retrieved from https://escholarship.umassmed.edu/oapubs/3964
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