Accession Number : AD1033874


Title :   Msi2 Regulates the Aggressiveness of Non Small Cell Lung Cancer (NSCLC)


Descriptive Note : Technical Report,15 Sep 2015,14 Sep 2016


Corporate Author : University of New Mexico Albuquerque United States


Personal Author(s) : Boumber,Yanis


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1033874.pdf


Report Date : 01 Oct 2016


Pagination or Media Count : 77


Abstract : Purpose, scope: The objective of this project is to expand our mechanistic data to characterize the functional roles of MSI2 in human NSCLC cells and test whether MSI2-overexpressing cells are more sensitive to gamma-secretase and TGF-Beta receptor Type I kinase (TGF-BetaRI) inhibitors(Aim 1). I also aim to investigate if MSI2 expression is clinically predictive in tumor specimens from lung cancer patients (Aim 2). Major findings and progress: Depletion of MSI2 in multiple independent metastatic murine and human NSCLC cell lines reduced invasion and metastatic potential, independent proliferation effects. MSI2 depletion significantly induced expression of proteins associated with epithelial identity, including tight junction claudin proteins and down-regulated direct translational targets associated with EMT, and unexpectedly upregulated NOTCH pathways. Depletion of TGFRBetaRI or SMAD3 resulted in reduced invasion, while overexpression of TGFBetaRI reversed the loss of invasion associated with MSI2 depletion. Interestingly, MSI2 depletion reduced E-cadherin expression, while increasing fibronectin (FN1), reflecting a mixed epithelialmesenchymal phenotype. MSI2 provides essential support for TGFBetaR1/SMAD3 signaling, contributes to NSCLC progression and may be a predictive biomarker of NSCLC aggressiveness. TGF-BetaRI and gamma-secretase drug studies in vitro and in vivo are ongoing, while immunohistochemistry studies are starting Fall 2016.


Descriptors :   Lung cancer , metastasis , TISSUE ARRAY ANALYSIS


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE