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SOX7 is down-regulated in lung cancer
Takahide Hayano1, Manoj Garg, Dong Yin
1Genomic Oncology Programme, Cancer Science Institute of Singapore, Singapore, Singapore.
Background:
SOX7 is a transcription factor belonging to the SOX family. Its role in lung cancer is unknown.
Methods:
In this study, whole genomic copy number analysis was performed on a series of non-small cell lung cancer (NSCLC) cell lines and samples from individuals with epidermal growth factor receptor (EGFR) mutations using a SNP-Chip platform. SOX7 was measured in NSCLC samples and cell lines, and forced expressed in one of these lines.
Results:
A notable surprise was that the numerous copy number (CN) changes observed in samples of Asian, non-smoking EGFR mutant NSCLC were nearly the same as those CN alterations seen in a large collection of NSCLC from The Cancer Genome Atlas which is presumably composed of predominantly Caucasians who often smoked. However, four regions had CN changes fairly unique to the Asian EGFR mutant group. We also examined CN changes in NSCLC lines. The SOX7 gene was homozygously deleted in one (HCC2935) of 10 NSCLC cell lines and heterozygously deleted in two other NSCLC lines. Expression of SOX7 was significantly downregulated in NSCLC cell lines (8/10, 80%) and a large collection of NSCLC samples compared to matched normal lung (57/62, 92%, p= 0.0006). Forced-expression of SOX7 in NSCLC cell lines markedly reduced their cell growth and enhanced their apoptosis.
Conclusion:
These data suggest that SOX7 is a novel tumor suppressor gene silenced in the majority of NSCLC samples.
Insights
SOX7, a transcription factor, acts as a novel tumor suppressor in non-small cell lung cancer (NSCLC). Its downregulation is frequent in NSCLC, and restoring SOX7 expression inhibits tumor cell growth and promotes apoptosis.
Area of Science:
- Genetics and Molecular Biology
- Oncology
- Cancer Genomics
Background:
- SOX7 is a transcription factor within the SOX family.
- The specific role of SOX7 in lung cancer pathogenesis remains largely unexplored.
Purpose of the Study:
- To investigate the function of SOX7 in non-small cell lung cancer (NSCLC).
- To determine the copy number alterations and expression patterns of SOX7 in NSCLC.
- To evaluate the impact of SOX7 modulation on NSCLC cell behavior.
Main Methods:
- Whole genomic copy number analysis using SNP-Chip platform on NSCLC cell lines and patient samples with EGFR mutations.
- Quantification of SOX7 gene expression in NSCLC samples and cell lines.
- Forced expression of SOX7 in NSCLC cell lines to assess its functional effects.
Main Results:
- Copy number (CN) alterations in Asian, non-smoking EGFR-mutant NSCLC showed similarities to The Cancer Genome Atlas (TCGA) collection, with some unique regions.
- The SOX7 gene was found to be homozygously deleted in 1 NSCLC cell line and heterozygously deleted in 2 others.
- SOX7 expression was significantly downregulated in 80% of NSCLC cell lines and 92% of NSCLC samples compared to normal lung tissue (p=0.0006).
- Forced expression of SOX7 markedly reduced cell growth and enhanced apoptosis in NSCLC cell lines.
Conclusions:
- SOX7 functions as a novel tumor suppressor gene in non-small cell lung cancer.
- Silencing or deletion of SOX7 is a common event in the majority of NSCLC cases.
- Restoration of SOX7 expression has therapeutic potential for NSCLC.
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