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YBX1/YB-1 induces partial EMT and tumourigenicity through secretion of angiogenic factors into the extracellular microenvironment

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posted on 04.08.2021, 07:40 by SK Gopal, David GreeningDavid Greening, RA Mathias, H Ji, A Rai, Maoshan Chen, H-J Zhu, Richard SimpsonRichard Simpson
Epithelial-mesenchymal transition (EMT) describes a morphogenetic program which confers mesenchymal cell properties, such as reduced cell-cell contact and increased cell migration and invasion, to epithelial cells. Here we investigate the role of the pleiotropic transcription/splicing factor and RNA-binding protein nucleasesensitive element-binding protein 1 (YBX1/YB-1) in increasing the oncogenic potential of epithelial MDCK cells. Characterization of MDCK cells expressing YBX1 (MDCKYBX1 cells) revealed a partial EMT phenotype, including cytosolic relocalization of E-cadherin, increased cell scattering, and anchorage-independent growth. Subcutaneous injection of parental MDCK cells into NOD/SCID mice did not form tumours. Critically, MDCKYBX1 cells established viable tumour xenografts, and immunohistochemical staining indicated murine vascularization by CD31+ endothelial cells. We analysed the total secretome (containing soluble and extracellular vesicles) of MDCKYBX1 cells to investigate regulation of the tumour microenvironment. YBX1 expression elevated release of secreted factors known to enhance angiogenesis (TGF-β, CSF-1, NGF, VGF, ADAM9 and ADAM17), compared to MDCK cells. Importantly, treatment with MDCKYBX1 cell-derived secretome increased recipient 2F-2B endothelial cell motility. This defines YBX1 as an oncogenic enhancer that can regulate tumour angiogenesis via release of secreted modulators into the extracellular microenvironment.

Funding

The authors are supported, in part, by the National Health and Medical Research Council of Australia program grant 487922 (R.J.S.), project grant 1057741 (R.J.S), 628727 (HJ.Z), Melbourne Research Grant Support Scheme (Melbourne University, HJ.Z) and Early Career CJ Martin Fellowship APP1037043 (R.A.M.). S.K.G/A.R/M.C are supported by La Trobe University Postgraduate Scholarships. The authors would like to thank Dr. Jacqueline Orian for assistance with immunohistochemistry. Proteomics in this study was supported using the LIMS Mass Spectrometry and Proteomics facility.

History

Publication Date

23/04/2015

Journal

Oncotarget

Volume

6

Issue

15

Pagination

13p. (p. 13718-13730)

Publisher

Impact Journals

ISSN

1949-2553

Rights Statement

The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.

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