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| Status |
Public on May 16, 2015 |
| Title |
Targeting the novel SALL4/CBL-B pathway by HDAC inhibitor MS-275 in lung cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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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| Overall design |
Cells from human lung carcinoma cell line H661 with wildtype scrambled controls or Sall4 knockdown were used for RNA extraction and hybridization on Affymetrix microarrays.
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| Contributor(s) |
Yong KJ, Li A, Ou W, Zhao W, Wang F, Tatetsu H, Yan BS, Qi L, Fletcher J, Yang H, Soo R, Tenen DG, Li C |
| Citation(s) |
27705911 |
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| Submission date |
May 15, 2015 |
| Last update date |
Oct 05, 2018 |
| Contact name |
Henry Yang |
| E-mail(s) |
csiyangh@nus.edu.sg
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| Organization name |
Cancer Science Institute of Singapore
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| Street address |
28 Medical Drive
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| City |
Singapore |
| ZIP/Postal code |
117456 |
| Country |
Singapore |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| GSM1688794 |
Lung cancer cell H661 with scrambled control , rep1 |
| GSM1688795 |
Lung cancer cell H661 with scrambled control , rep2 |
| GSM1688796 |
Lung cancer cell H661 with scrambled control , rep3 |
| GSM1688797 |
Lung cancer cell H661 with SALL4 shRNA , rep1 |
| GSM1688798 |
Lung cancer cell H661 with SALL4 shRNA , rep2 |
| GSM1688799 |
Lung cancer cell H661 with SALL4 shRNA , rep3 |
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| Relations |
| BioProject |
PRJNA284164 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE68959_RAW.tar |
20.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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