Stromal cell extracellular vesicular cargo mediated regulation of breast cancer cell metastasis via ubiquitin conjugating enzyme E2 N pathway.

Autor:	Vallabhaneni KC; Cancer Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA.; Department of Radiation Oncology, University of Mississippi Medical Center, Jackson, MS 39216, USA., Penfornis P; Cancer Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA., Xing F; Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA., Hassler Y; Cancer Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA., Adams KV; Department of Pathology, University of Mississippi Medical Center, Jackson, MS 39216, USA., Mo YY; Cancer Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA., Watabe K; Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.; Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA., Pochampally R; Cancer Institute, University of Mississippi Medical Center, Jackson, MS 39216, USA.; Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS 39216, USA.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2017 Nov 10; Vol. 8 (66), pp. 109861-109876. Date of Electronic Publication: 2017 Nov 10 (Print Publication: 2017).
DOI:	10.18632/oncotarget.22371
Abstrakt:	Mesenchymal stromal cells (hMSCs) have been used to understand the stromal cell properties in solid tumors because of their ablity to differentiate into most cell types. We investigated the role of EVs from hMSCs (hMSC-EVs) in breast cancer metastasis using MDA-MB-231 parental cell line and organotropic sub-lines. We demonstrated that hMSC-EVs significantly suppressed the metastatic potential of the parental cell line when compared to their organotropic sublines. hMSC-EVs induce dormancy in the parental cell line but not in their organotropic sub-lines and miR-205 and miR-31 from EV cargo played a role. Further, Ubiquitin Conjugating Enzyme E2 N (UBE2N/Ubc13) - metastasis-regulating gene, is a target of these miRNAs and silencing of UBE2N/Ubc13 expression significantly suppressed migration, invasion, and proliferation of breast cancer cells. To summarize, hMSC-EVs support primary breast tumor progression but suppress the metastasis of breast cancer cells that are not organ-committed through the UBE2N/Ubc13 pathway and play a role in premetastic niche formation. Competing Interests: CONFLICTS OF INTEREST The authors declare that there no conflicts of interest exist.
Databáze:	MEDLINE
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