Skip to main content
Erschienen in: Tumor Biology 9/2016

01.06.2016 | Original Article

Sex-determining region Y-box3 (SOX3) functions as an oncogene in promoting epithelial ovarian cancer by targeting Src kinase

verfasst von: Qin Yan, Fangyuan Wang, Yi Miao, Xiaomei Wu, Mingzhu Bai, Xiaowei Xi, Youji Feng

Erschienen in: Tumor Biology | Ausgabe 9/2016

Einloggen, um Zugang zu erhalten

Abstract

Ovarian cancer is one of the most common cancers which cause female mortality. The knowledge of ovarian cancer initiation and progression is critical to develop new therapeutic strategies to treat and prevent it. Recently, SOX3 has been reported to play a pivotal role in tumor progression. However, the clinical significance of SOX3 in human ovarian cancer remains elusive, and the identity of SOX3 in ovarian cancer initiation, progression, and the related underlying mechanism is unknown. In this study, we showed that SOX3 expression increased from benign and borderline to malignant ovarian tumors. Subsequently, we found that overexpression of SOX3 in EOC cells promoted proliferation, migration, and invasion, while restrained apoptosis and adhesion of ovarian cancer cells. In contrast, silencing of SOX3 gained the opposite results. Finally, we discovered SOX3 targeted Src kinase in EOC cells. These data imply that SOX3, acting as an oncogene in EOC, is not only a crucial factor in the carcinogenesis but also a promising therapeutic target for EOC.
Literatur
4.
Zurück zum Zitat Stevanovic M, Lovell-Badge R, Collignon J, Goodfellow PN. SOX3 is an X-linked gene related to SRY. Hum Mol Genet. 1993;2(12):2013–8.CrossRefPubMed Stevanovic M, Lovell-Badge R, Collignon J, Goodfellow PN. SOX3 is an X-linked gene related to SRY. Hum Mol Genet. 1993;2(12):2013–8.CrossRefPubMed
5.
Zurück zum Zitat Uchikawa M, Kamachi Y, Kondoh H. Two distinct subgroups of group B sox genes for transcriptional activators and repressors: their expression during embryonic organogenesis of the chicken. Mech Dev. 1999;84(1–2):103–20.CrossRefPubMed Uchikawa M, Kamachi Y, Kondoh H. Two distinct subgroups of group B sox genes for transcriptional activators and repressors: their expression during embryonic organogenesis of the chicken. Mech Dev. 1999;84(1–2):103–20.CrossRefPubMed
6.
Zurück zum Zitat Bowles J, Schepers G, Koopman P. Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators. Dev Biol. 2000;227(2):239–55.CrossRefPubMed Bowles J, Schepers G, Koopman P. Phylogeny of the SOX family of developmental transcription factors based on sequence and structural indicators. Dev Biol. 2000;227(2):239–55.CrossRefPubMed
7.
Zurück zum Zitat Kelberman D, Rizzoti K, Lovell-Badge R, Robinson ICAF, Dattani MT. Genetic regulation of pituitary gland development in human and mouse. Endocr Rev. 2009;30(7):790–829.CrossRefPubMedPubMedCentral Kelberman D, Rizzoti K, Lovell-Badge R, Robinson ICAF, Dattani MT. Genetic regulation of pituitary gland development in human and mouse. Endocr Rev. 2009;30(7):790–829.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Pevny LH, Lovell-Badge R. Sox genes find their feet. Curr Opin Genet Dev. 1997;7(3):338–44.CrossRefPubMed Pevny LH, Lovell-Badge R. Sox genes find their feet. Curr Opin Genet Dev. 1997;7(3):338–44.CrossRefPubMed
10.
Zurück zum Zitat Alatzoglou KS, Azriyanti A, Rogers N, Ryan F, Curry N, Noakes C, et al. SOX3 deletion in mouse and human is associated with persistence of the craniopharyngeal canal. J Clin Endocrinol Metab. 2014;99(12):E2702–8.CrossRefPubMed Alatzoglou KS, Azriyanti A, Rogers N, Ryan F, Curry N, Noakes C, et al. SOX3 deletion in mouse and human is associated with persistence of the craniopharyngeal canal. J Clin Endocrinol Metab. 2014;99(12):E2702–8.CrossRefPubMed
11.
Zurück zum Zitat Bylund M, Andersson E, Novitch BG, Muhr J. Vertebrate neurogenesis is counteracted by Sox1-3 activity. Nat Neurosci. 2003;6(11):1162–8.CrossRefPubMed Bylund M, Andersson E, Novitch BG, Muhr J. Vertebrate neurogenesis is counteracted by Sox1-3 activity. Nat Neurosci. 2003;6(11):1162–8.CrossRefPubMed
12.
Zurück zum Zitat Laronda MM, Jameson JL. Sox3 functions in a cell-autonomous manner to regulate spermatogonial differentiation in mice. Endocrinology. 2011;152(4):1606–15.CrossRefPubMedPubMedCentral Laronda MM, Jameson JL. Sox3 functions in a cell-autonomous manner to regulate spermatogonial differentiation in mice. Endocrinology. 2011;152(4):1606–15.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Brunelli S, Silva Casey E, Bell D, Harland R, Lovell-Badge R. Expression of Sox3 throughout the developing central nervous system is dependent on the combined action of discrete, evolutionarily conserved regulatory elements. Genesis. 2003;36(1):12–24.CrossRefPubMed Brunelli S, Silva Casey E, Bell D, Harland R, Lovell-Badge R. Expression of Sox3 throughout the developing central nervous system is dependent on the combined action of discrete, evolutionarily conserved regulatory elements. Genesis. 2003;36(1):12–24.CrossRefPubMed
14.
Zurück zum Zitat Kovacevic-Grujicic N, Mojsin M, Popovic J, Petrovic I, Topalovic V, Stevanovic M. Cyclic AMP response element binding (CREB) protein acts as a positive regulator of SOX3 gene expression in NT2/D1 cells. BMB Rep. 2014;47(4):197–202.CrossRefPubMedPubMedCentral Kovacevic-Grujicic N, Mojsin M, Popovic J, Petrovic I, Topalovic V, Stevanovic M. Cyclic AMP response element binding (CREB) protein acts as a positive regulator of SOX3 gene expression in NT2/D1 cells. BMB Rep. 2014;47(4):197–202.CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Xia Y, Papalopulu N, Vogt PK, Li J. The oncogenic potential of the high mobility group box protein Sox3. Cancer Res. 2000;60(22):6303–6.PubMed Xia Y, Papalopulu N, Vogt PK, Li J. The oncogenic potential of the high mobility group box protein Sox3. Cancer Res. 2000;60(22):6303–6.PubMed
16.
Zurück zum Zitat Kim R, Trubetskoy A, Suzuki T, Jenkins NA, Copeland NG, Lenz J. Genome-based identification of cancer genes by proviral tagging in mouse retrovirus-induced T-cell lymphomas. J Virol. 2003;77(3):2056–62.CrossRefPubMedPubMedCentral Kim R, Trubetskoy A, Suzuki T, Jenkins NA, Copeland NG, Lenz J. Genome-based identification of cancer genes by proviral tagging in mouse retrovirus-induced T-cell lymphomas. J Virol. 2003;77(3):2056–62.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Bocker W. [WHO classification of breast tumors and tumors of the female genital organs: pathology and genetics]. WHO-klassifikation der tumoren der mamma und des weiblichen genitale: pathologie und genetik. Verh Dtsch Ges Pathol. 2002;86:116–9.PubMed Bocker W. [WHO classification of breast tumors and tumors of the female genital organs: pathology and genetics]. WHO-klassifikation der tumoren der mamma und des weiblichen genitale: pathologie und genetik. Verh Dtsch Ges Pathol. 2002;86:116–9.PubMed
18.
Zurück zum Zitat Gure AO, Stockert E, Scanlan MJ, Keresztes RS, Jager D, Altorki NK, et al. Serological identification of embryonic neural proteins as highly immunogenic tumor antigens in small cell lung cancer. Proc Natl Acad Sci U S A. 2000;97(8):4198–203.CrossRefPubMedPubMedCentral Gure AO, Stockert E, Scanlan MJ, Keresztes RS, Jager D, Altorki NK, et al. Serological identification of embryonic neural proteins as highly immunogenic tumor antigens in small cell lung cancer. Proc Natl Acad Sci U S A. 2000;97(8):4198–203.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Li K, Wang R-W, Jiang Y-G, Zou Y-B, Guo W. Overexpression of Sox3 is associated with diminished prognosis in esophageal squamous cell carcinoma. Ann Surg Oncol. 2013;20(Suppl 3):S459–66.CrossRefPubMed Li K, Wang R-W, Jiang Y-G, Zou Y-B, Guo W. Overexpression of Sox3 is associated with diminished prognosis in esophageal squamous cell carcinoma. Ann Surg Oncol. 2013;20(Suppl 3):S459–66.CrossRefPubMed
20.
Zurück zum Zitat Acloque H, Ocana OH, Matheu A, Rizzoti K, Wise C, Lovell-Badge R, et al. Reciprocal repression between Sox3 and snail transcription factors defines embryonic territories at gastrulation. Dev Cell. 2011;21(3):546–58.CrossRefPubMedPubMedCentral Acloque H, Ocana OH, Matheu A, Rizzoti K, Wise C, Lovell-Badge R, et al. Reciprocal repression between Sox3 and snail transcription factors defines embryonic territories at gastrulation. Dev Cell. 2011;21(3):546–58.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Kovacevic Grujicic N, Mojsin M, Krstic A, Stevanovic M. Functional characterization of the human SOX3 promoter: identification of transcription factors implicated in basal promoter activity. Gene. 2005;344:287–97.CrossRefPubMed Kovacevic Grujicic N, Mojsin M, Krstic A, Stevanovic M. Functional characterization of the human SOX3 promoter: identification of transcription factors implicated in basal promoter activity. Gene. 2005;344:287–97.CrossRefPubMed
22.
Zurück zum Zitat Hu X, Wu X, Xu J, Zhou J, Han X, Guo J. Src kinase up-regulates the ERK cascade through inactivation of protein phosphatase 2 A following cerebral ischemia. BMC Neurosci. 2009;10:74.CrossRefPubMedPubMedCentral Hu X, Wu X, Xu J, Zhou J, Han X, Guo J. Src kinase up-regulates the ERK cascade through inactivation of protein phosphatase 2 A following cerebral ischemia. BMC Neurosci. 2009;10:74.CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Kopetz S, Shah AN, Gallick GE. Src continues aging: current and future clinical directions. Clin Cancer Res. 2007;13(24):7232–6.CrossRefPubMed Kopetz S, Shah AN, Gallick GE. Src continues aging: current and future clinical directions. Clin Cancer Res. 2007;13(24):7232–6.CrossRefPubMed
25.
Zurück zum Zitat Kim LC, Song L, Haura EB. Src kinases as therapeutic targets for cancer. Nat Rev Clin Oncol. 2009;6(10):587–95.CrossRefPubMed Kim LC, Song L, Haura EB. Src kinases as therapeutic targets for cancer. Nat Rev Clin Oncol. 2009;6(10):587–95.CrossRefPubMed
26.
Zurück zum Zitat Irby RB, Yeatman TJ. Role of Src expression and activation in human cancer. Oncogene. 2000;19(49):5636–42.CrossRefPubMed Irby RB, Yeatman TJ. Role of Src expression and activation in human cancer. Oncogene. 2000;19(49):5636–42.CrossRefPubMed
27.
Zurück zum Zitat Bromann PA, Korkaya H, Courtneidge SA. The interplay between Src family kinases and receptor tyrosine kinases. Oncogene. 2004;23(48):7957–68.CrossRefPubMed Bromann PA, Korkaya H, Courtneidge SA. The interplay between Src family kinases and receptor tyrosine kinases. Oncogene. 2004;23(48):7957–68.CrossRefPubMed
28.
Zurück zum Zitat Abram CL, Courtneidge SA. Src family tyrosine kinases and growth factor signaling. Exp Cell Res. 2000;254(1):1–13.CrossRefPubMed Abram CL, Courtneidge SA. Src family tyrosine kinases and growth factor signaling. Exp Cell Res. 2000;254(1):1–13.CrossRefPubMed
Metadaten
Titel
Sex-determining region Y-box3 (SOX3) functions as an oncogene in promoting epithelial ovarian cancer by targeting Src kinase
verfasst von
Qin Yan
Fangyuan Wang
Yi Miao
Xiaomei Wu
Mingzhu Bai
Xiaowei Xi
Youji Feng
Publikationsdatum
01.06.2016
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 9/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5095-x

Weitere Artikel der Ausgabe 9/2016

Tumor Biology 9/2016 Zur Ausgabe

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

CUP-Syndrom: Künstliche Intelligenz kann Primärtumor finden

30.04.2024 Künstliche Intelligenz Nachrichten

Krebserkrankungen unbekannten Ursprungs (CUP) sind eine diagnostische Herausforderung. KI-Systeme können Pathologen dabei unterstützen, zytologische Bilder zu interpretieren, um den Primärtumor zu lokalisieren.

Sind Frauen die fähigeren Ärzte?

30.04.2024 Gendermedizin Nachrichten

Patienten, die von Ärztinnen behandelt werden, dürfen offenbar auf bessere Therapieergebnisse hoffen als Patienten von Ärzten. Besonders gilt das offenbar für weibliche Kranke, wie eine Studie zeigt.

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.