Abstract
Our previous work identified a 13-gene miRNA signature predictive of response to the epidermal growth factor receptor (EGFR) inhibitor, erlotinib, in Non-Small Cell Lung Cancer cell lines. Bioinformatic analysis of the signature showed a functional convergence on TGFβ canonical signalling. We hypothesized that TGFβ signalling controls expression of the miRNA genes comprising an erlotinib response signature in NSCLC. Western analysis revealed that TGFβ signalling via Smad2/3/4 occurred differently between erlotinib-resistant A549 and erlotinib- sensitive PC9 cells. We showed that TGFβ induced an interaction between Smad4 and putative Smad Binding Elements in PC9. However, qRT-PCR analysis showed that endogenous miR-140/141/200c expression changes resulted from time in treatments, not the treatments themselves. Moreover, flow cytometry indicated that cells exited the cell cycle in the same manner. Taken together these data indicated that the miRNA comprising the signature are likely regulated by the cell cycle rather than by TGFβ. Importantly, this work revealed that TGFβ did not induce EMT in PC9 cells, but rather TGFβ-inhibition induced an EMT-intermediate. These data also show that growth/proliferation signals by constitutively-activated EGFR may rely on TGFβ and a possible relationship between TGFβ and EGFR signalling may prevent EMT progression in this context rather than promote it.
Document Type
Article
Publication Date
6-23-2017
Digital Object Identifier (DOI)
https://doi.org/10.1038/s41598-017-04097-7
Related Content
Supplementary information accompanies this paper at doi:10.1038/s41598-017-04097-7
Repository Citation
Krentz Gober, Madeline J.; Collard, James P.; Thompson, Katherine L.; and Black, Esther P., "A MicroRNA Signature of Response to Erlotinib is Descriptive of TGFβ Behaviour in NSCLC" (2017). Pharmaceutical Sciences Faculty Publications. 83.
https://uknowledge.uky.edu/ps_facpub/83
Supplementary Figures
41598_2017_4097_MOESM2_ESM.csv (4 kB)
Supplementary Data Set 1
Notes/Citation Information
Published in Scientific Reports, v. 7, article 4202, p. 1-12.
© The Author(s) 2017
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