4.6 Article

SOX14 activates the p53 signaling pathway and induces apoptosis in a cervical carcinoma cell line

Journal

PLOS ONE
Volume 12, Issue 9, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0184686

Keywords

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Funding

  1. Ministry of Education, Science and Technological Development, Republic of Serbia [173051]
  2. Serbian Academy of Sciences and Arts (Project: Studying the molecular mechanisms involved in maintaining pluripotency and differentiation of stem cells [F 24]
  3. Northwestern University RHLCCC Flow Cytometry Facility
  4. Cancer Center Support Grant [NCI CA060553]
  5. NATIONAL CANCER INSTITUTE [P30CA060553] Funding Source: NIH RePORTER

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SOX14 is a member of the SOX family of transcription factors mainly involved in the regulation of neural development. Recently, it became evident that SOX14 is one of four hyper-methylated genes in cervical carcinoma, considered as a tumor suppressor candidate in this type of malignancy. In this paper we elucidated the role of SOX14 in the regulation of malignant properties of cervical carcinoma cells in vitro. Functional analysis performed in HeLa cells revealed that SOX14 overexpression decreased viability and promoted apoptosis through altering the expression of apoptosis related genes. Our results demonstrated that overexpression of SOX14 initiated accumulation of p53, demonstrating potential cross-talk between SOX14 and the p53 signaling pathway. Further analysis unambiguously showed that SOX14 triggered posttranslational modification of p53 protein, as detected by the significantly increased level of phospho-p53 (Ser-15) in SOX14-overexpressing HeLa cells. Moreover, the obtained results revealed that SOX14 activated p53 protein, which was confirmed by elevated p21 Waf1/Cip1, a well known target gene of p53. This study advances our understanding about the role of SOX14 and might explain the molecular mechanism by which this transcription factor could exert tumor suppressor properties in cervical carcinoma.

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