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Accession IconGSE68959

Targeting the novel SALL4/CBL-B pathway by HDAC inhibitor MS-275 in lung cancer

Organism Icon Homo sapiens
Sample Icon 6 Downloadable Samples
Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

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The overall survival of lung cancer patients remains dismal despite the availability of targeted therapies. Oncofetal protein SALL4 is a novel cancer target. We herein report that SALL4 was aberrantly expressed in a subset of lung cancer patients with poor survival. SALL4 silencing by RNA interference or SALL4 peptide inhibitor treatment led to impaired lung cancer cell growth. Expression profiling on SALL4-knockdown cells demonstrated that both the EGFR and IGF1R signaling pathways were affected. Further studies revealed that SALL4 suppresses these pathways indirectly by repressing CBL-B. Connectivity Map analysis revealed HDAC inhibitor MS-275 as a potential drug in treating SALL4-expressing cancers and this was confirmed using 17 lung cancer cell lines. In summary, we report for the first time that MS-275 can target the novel SALL4/CBL-B pathway in lung cancer. This lays the foundation for future clinical studies to evaluate the therapeutic efficacy of MS-275 in SALL4-positive lung cancer patients.
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