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Title: Bosutinib inhibits migration and invasion via ack1 in kras mutant non-small cell lung cancer
Authors: Tan, D.S.W
Haaland, B 
Gan, J.M
Tham, S.C
Sinha, I
Tan, E.H
Lim, K.H 
Takano, A 
Krisna, S.S
Thu, M.M.M
Liew, H.P
Ullrich, A
Lim, W.-T 
Chua, B.T
Keywords: Aniline Compounds
Antineoplastic Agents
Blotting, Western
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
Cell Movement
Gene Knockdown Techniques
Lung Neoplasms
Neoplasm Invasiveness
Protein-Tyrosine Kinases
Proto-Oncogene Proteins
ras Proteins
Real-Time Polymerase Chain Reaction
Tissue Array Analysis
Xenograft Model Antitumor Assays
Issue Date: 2014
Citation: Tan, D.S.W, Haaland, B, Gan, J.M, Tham, S.C, Sinha, I, Tan, E.H, Lim, K.H, Takano, A, Krisna, S.S, Thu, M.M.M, Liew, H.P, Ullrich, A, Lim, W.-T, Chua, B.T (2014). Bosutinib inhibits migration and invasion via ack1 in kras mutant non-small cell lung cancer. Molecular Cancer 13 (1) : 13. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: The advent of effective targeted therapeutics has led to increasing emphasis on precise biomarkers for accurate patient stratification. Here, we describe the role of ACK1, a non-receptor tyrosine kinase in abrogating migration and invasion in KRAS mutant lung adenocarcinoma. Bosutinib, which inhibits ACK1 at 2.7 nM IC50, was found to inhibit cell migration and invasion but not viability in a panel of non-small cell lung cancer (NSCLC) cell lines. Knockdown of ACK1 abrogated bosutinib-induced inhibition of cell migration and invasion specifically in KRAS mutant cells. This finding was further confirmed in an in vivo zebrafish metastatic model. Tissue microarray data on 210 Singaporean lung adenocarcinomas indicate that cytoplasmic ACK1 was significantly over-expressed relative to paired adjacent non-tumor tissue. Interestingly, ACK1 expression in " normal" tissue adjacent to tumour, but not tumour, was independently associated with poor overall and relapse-free survival. In conclusion, inhibition of ACK1 with bosutinib attenuates migration and invasion in the context of KRAS mutant NSCLC and may fulfil a therapeutic niche through combinatorial treatment approaches. © 2014 Tan et al.; licensee BioMed Central Ltd.
Source Title: Molecular Cancer
ISSN: 14764598
DOI: 10.1186/1476-4598-13-13
Rights: Attribution 4.0 International
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