SOX2 suppresses CDKN1A to sustain growth of lung squamous cell carcinoma

Takuya Fukazawa, Minzhe Guo, Naomasa Ishida, Tomoki Yamatsuji, Munenori Takaoka, Etsuko Yokota, Minoru Haisa, Noriko Miyake, Tomoko Ikeda, Tatsuo Okui, Nagio Takigawa, Yutaka Maeda, Yoshio Naomoto

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Since the SOX2 amplification was identified in lung squamous cell carcinoma (lung SCC), SOX2 transcriptional downstream targets have been actively investigated; however, such targets are often cell line specific. Here, in order to identify highly consensus SOX2 downstream genes in lung SCC cells, we used RNA-seq data from 178 lung SCC specimens (containing tumor and tumor-associated cells) and analyzed the correlation between SOX2 and previously-reported SOX2-controlled genes in lung SCC. In addition, we used another RNA-seq dataset from 105 non-small cell lung cancer cell lines (NSCLC; including 4 lung SCC cell lines) and again analyzed the correlation between SOX2 and the reported SOX2-controlled genes in the NSCLC cell lines (no tumor-associated cells). We combined the two analyses and identified genes commonly correlated with SOX2 in both datasets. Among the 99 genes reported as SOX2 downstream and/or correlated genes, we found 4 negatively-correlated (e.g., CDKN1A) and 11 positively-correlated genes with SOX2. We used biological studies to demonstrate that CDKN1A was suppressed by SOX2 in lung SCC cells. G1 cell cycle arrest induced by SOX2 siRNA was rescued by CDKN1A siRNA. These results indicate that the tumorigenic effect of SOX2 in lung SCC cells is mediated in part by suppression of CDKN1A.

Original languageEnglish
Article number20113
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Feb 5 2016
Externally publishedYes

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Squamous Cell Carcinoma
Lung
Growth
Genes
Cell Line
Small Interfering RNA
RNA
G1 Phase Cell Cycle Checkpoints
Tumor Cell Line
Non-Small Cell Lung Carcinoma
Neoplasms

ASJC Scopus subject areas

  • General

Cite this

Fukazawa, T., Guo, M., Ishida, N., Yamatsuji, T., Takaoka, M., Yokota, E., ... Naomoto, Y. (2016). SOX2 suppresses CDKN1A to sustain growth of lung squamous cell carcinoma. Scientific Reports, 6, [20113]. https://doi.org/10.1038/srep20113

SOX2 suppresses CDKN1A to sustain growth of lung squamous cell carcinoma. / Fukazawa, Takuya; Guo, Minzhe; Ishida, Naomasa; Yamatsuji, Tomoki; Takaoka, Munenori; Yokota, Etsuko; Haisa, Minoru; Miyake, Noriko; Ikeda, Tomoko; Okui, Tatsuo; Takigawa, Nagio; Maeda, Yutaka; Naomoto, Yoshio.

In: Scientific Reports, Vol. 6, 20113, 05.02.2016.

Research output: Contribution to journalArticle

Fukazawa, T, Guo, M, Ishida, N, Yamatsuji, T, Takaoka, M, Yokota, E, Haisa, M, Miyake, N, Ikeda, T, Okui, T, Takigawa, N, Maeda, Y & Naomoto, Y 2016, 'SOX2 suppresses CDKN1A to sustain growth of lung squamous cell carcinoma', Scientific Reports, vol. 6, 20113. https://doi.org/10.1038/srep20113
Fukazawa T, Guo M, Ishida N, Yamatsuji T, Takaoka M, Yokota E et al. SOX2 suppresses CDKN1A to sustain growth of lung squamous cell carcinoma. Scientific Reports. 2016 Feb 5;6. 20113. https://doi.org/10.1038/srep20113
Fukazawa, Takuya ; Guo, Minzhe ; Ishida, Naomasa ; Yamatsuji, Tomoki ; Takaoka, Munenori ; Yokota, Etsuko ; Haisa, Minoru ; Miyake, Noriko ; Ikeda, Tomoko ; Okui, Tatsuo ; Takigawa, Nagio ; Maeda, Yutaka ; Naomoto, Yoshio. / SOX2 suppresses CDKN1A to sustain growth of lung squamous cell carcinoma. In: Scientific Reports. 2016 ; Vol. 6.
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