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Inhibition of Hedgehog signaling sensitizes NSCLC cells to standard therapies through modulation of EMT-regulating miRNAs
Conclusions: We demonstrate that Hh pathway, through EMT-induction, leads to reduced sensitivity to EGFR-TKIs in NSCLCs. Therefore, targeting Hh pathway may lead to the reversal of EMT phenotype and improve the therapeutic efficacy of EGFR-TKIs in NSCLC patients.
Source: Journal of Hematology and Oncology - October 7, 2013 Category: Hematology Authors: Aamir AhmadMa¿in MaitahKevin GinnebaughYiwei LiBin BaoShirish GadgeelFazlul Sarkar Source Type: research

Mechanism of c-Met and EGFR tyrosine kinase inhibitor resistance through epithelial mesenchymal transition in non-small cell lung cancer.
Abstract According to Cancer Research UK currently available estimates, 14.1 million new lung cancer cases were diagnosed and a staggering 8.2 million people worldwide died from lung cancer in 2012. EGFR and c-Met are two tyrosine kinase receptors most commonly overexpressed or mutated in Non-small Cell Lung Cancer (NSCLC) resulting in increased proliferation and survival of lung cancer cells. Tyrosine kinase inhibitors (TKIs), such as Erlotinib, approved by the FDA as first/second line therapy for NSCLC patients have limited clinical efficacy due to acquired resistance. In this manuscript, we investigate and disc...
Source: Biochemical and Biophysical Research communications - July 6, 2016 Category: Biochemistry Authors: Rastogi I, Rajanna S, Webb A, Chhabra G, Foster B, Webb B, Puri N Tags: Biochem Biophys Res Commun Source Type: research

Comparison of epithelial mesenchymal transition mediated tyrosine kinase inhibitor resistance in non-small cell lung cancer cell lines with wild type EGFR and mutant type EGFR.
This study investigates the role of epithelial-mesenchymal transition (EMT) in the development of resistance against TKIs in NSCLC. Currently, the role of p120-catenin, Kaiso factor and PRMT-1 in reversal of EMT in T790M mutated and TKI-resistant NSCLC cells is a new line of study. In this investigation we found upregulation of cytoplasmic p120-catenin, and it was co-localized with Kaiso factor. In the nucleus, binding of p120-catenin to Kaiso factor initiates transcription by activating EMT-transcription factors such as Snail, Slug, Twist, and ZEB1. PRMT-1 was also found to be upregulated, which induces methylation of Twi...
Source: Biochemical and Biophysical Research communications - January 11, 2018 Category: Biochemistry Authors: Iderzorig T, Kellen J, Osude C, Singh S, Woodman JA, Garcia C, Puri N Tags: Biochem Biophys Res Commun Source Type: research

Numb-associated kinases are required for SARS-CoV-2 infection and are cellular targets for antiviral strategies
Antiviral Res. 2022 Jun 20:105367. doi: 10.1016/j.antiviral.2022.105367. Online ahead of print.ABSTRACTThe coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose serious threats to global health. We previously reported that AAK1, BIKE and GAK, members of the Numb-associated kinase family, control intracellular trafficking of multiple RNA viruses during viral entry and assembly/egress. Here, using both genetic and pharmacological approaches, we probe the functional relevance of NAKs for SARS-CoV-2 infection. siRNA-mediated depletion of AAK1, ...
Source: Antiviral Research - June 23, 2022 Category: Virology Authors: Marwah Karim Sirle Saul Luca Ghita Malaya Kumar Sahoo Chengjin Ye Nishank Bhalla Chieh Wen Lo Jing Jin Jun-Gyu Park Bel én Martinez-Gualda Michael Patrick East Gary L Johnson Benjamin A Pinsky Luis Martinez-Sobrido Christopher R M Asquith Aarthi Narayana Source Type: research