Expression of teneurins is associated with tumor differentiation and patient survival in ovarian cancer

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dc.contributor.authorGraumann, Rebecca
dc.contributor.authorDi Capua, Gabriella A.
dc.contributor.authorOyarzún, Juan
dc.contributor.authorVásquez, Marcos A.
dc.contributor.authorLiao, Christine
dc.contributor.authorBrañes, Jorge A.
dc.contributor.authorRoa, Iván
dc.contributor.authorCasanello, Paola
dc.contributor.authorCorvalán, Alejandro H.
dc.contributor.authorOwen, Gareth
dc.contributor.authorDelgado, Iris
dc.contributor.authorUwe, Zangemeister-Wittke
dc.contributor.authorZiegler, Annemarie
dc.date.accessioned2017-08-29T17:53:44Z
dc.date.available2017-08-29T17:53:44Z
dc.date.issued2017
dc.description.abstractTeneurins are a family of highly conserved pair-rule proteins involved in morphogenesis and development of the central nervous system. Their function in adult tissues and in disease is largely unknown. Recent evidence suggests a role for dysregulated expression of Teneurins in human tumors, but systematic investigations are missing. Here, we investigated Teneurin-2 and Teneurin-4 expression in various cancer cell lines and in ovarian tumor tissues. Teneurin-2 and Teneurin-4 were expressed in most of the breast cancer cell lines tested. Teneurin-4 was also detected in ovarian cancer cell lines, and throughout ovarian tumors and normal ovary tissue. Ovarian tumors with low Teneurin-4 expression showed less differentiated phenotypes and these patients had shorter mean overall survival. Similarly, Teneurin-2 expression correlated with overall survival as well, especially in patients with serous tumors. In the various cell lines, 5-Aza-cytidine-induced changes in DNA methylation did not alter expression of Teneurin-2 and Teneurin-4, despite the existence of predicted CpG islands in both genes. Interestingly, however, we found evidence for the control of Teneurin-2 expression by the oncogenic growth factor FGF8. Furthermore, we identified multiple transcript splicing variants for Teneurin-2 and Teneurin-4, indicating complex gene expression patterns in malignant cells. Finally, downregulation of Teneurin-4 expression using siRNA caused a cell-type dependent increase in proliferation and resistance to cisplatin. Altogether, our data suggest that low Teneurin-4 expression provides a growth advantage to cancer cells and marks an undifferentiated state characterized by increased drug resistance and clinical aggressiveness. We conclude that Teneurin-2 and Teneurin-4 expression levels could be of prognostic value in ovarian cancer.
dc.format.extent24
dc.identifier.citationGraumann R, Di Capua GA, Oyarzún JE, Vásquez MA, Liao C, Brañes JA, Roa I, Casanello P, Corvalán AH, Owen GI, Delgado I, Zangemeister-Wittke U, Ziegler A. Expression of teneurins is associated with tumor differentiation and patient survival in ovarian cancer. PLoS One. 2017 May 4;12(5):e0177244.
dc.identifier.urihttp://hdl.handle.net/11447/1615
dc.identifier.urihttp://doi.org/10.1371/journal.pone.0177244
dc.language.isoen_US
dc.publisherPLoS
dc.subjectgene expression
dc.subjectPolymerase chain reaction
dc.subjectovarian cancer
dc.subjectdifferentiated tumors
dc.subjectsmall interfering RNAs
dc.subjectDNA methylation
dc.subjectMalignant tumors
dc.subjectReverse transcriptase-polymerase chain reaction
dc.titleExpression of teneurins is associated with tumor differentiation and patient survival in ovarian cancer
dc.typeArtículo

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