Dataset Information

C-Src functionality controls self-renewal, tumorigenicity and glucose metabolism in breast cancer stem cells

ABSTRACT: Deregulation of Src kinases is associated with cancer. We previously showed that SrcDN conditional expression in MCF7 cells diminished tumorigenesis and causes tumor regression in mice. However, it remained unclear whether SrcDN affected breast cancer stem cell functionality or it reduced tumor mass. Here, we address this question by isolating an enriched population of BCSCs (ESA+-CD44+-CD24-) and the tumor-differentiated cells (ESA+-CD44+-CD24+) from MCF7-Tet-On-SrcDN. ESA+-CD44+-CD24- grew in suspension forming mammospheres, and producing tumors in nude mice, while ESA+-CD44+-CD24+ were poorly/non-tumorigenic. Doxycycline-induction of SrcDN inhibited BCSC tumorigenesis, selfrenewal, and stem-cell markers expression. SrcDN significantly inhibited SFE, and stem-cell markers expression in triple-negative breast cancer (TNBC) MDA-MB-231 and SUM159PT cells. Inducible depletion of c-Src caused similar effects in MDA-MB-231 cells. In MCF7-Tet-On-SrcDN derived mammospheres SrcDN-induction inhibited expression, and activity of hexokinase, pyruvate kinase and lactate dehydrogenase, resulting in diminished glucose consumption and lactate production, which restricted Warburg effect. Thus, c-Src functionality is important for breast cancer stem cell maintenance and renewal, tumorigenicity, and stem cell transcription factor expression, effects linked to glucose metabolism reduction.

INSTRUMENT(S): TripleTOF 5600

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Sergio Ciordia

LAB HEAD: Jorge Martín Pérez

PROVIDER: PXD017789 | Pride | 2020-07-23

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	20160401_07_JMartin_iTRAQ_Fr1.wiff.zip	Wiff
	20160401_09_JMartin_iTRAQ_Fr2.wiff.zip	Wiff
	20160401_11_JMartin_iTRAQ_Fr3.wiff.zip	Wiff
	20160401_13_JMartin_iTRAQ_Fr4.wiff.zip	Wiff
	20160401_15_JMartin_iTRAQ_Fr5.wiff.zip	Wiff

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Publications

c-Src functionality controls self-renewal and glucose metabolism in MCF7 breast cancer stem cells.

Mayoral-Varo Víctor V Calcabrini Annarica A Sánchez-Bailón María Pilar MP Martínez-Costa Óscar H ÓH González-Páramos Cristina C Ciordia Sergio S Hardisson David D Aragón Juan J JJ Fernández-Moreno Miguel Ángel MÁ Martín-Pérez Jorge J

PloS one 20200716 7

Deregulation of Src kinases is associated with cancer. We previously showed that SrcDN conditional expression in MCF7 cells reduces tumorigenesis and causes tumor regression in mice. However, it remained unclear whether SrcDN affected breast cancer stem cell functionality or it reduced tumor mass. Here, we address this question by isolating an enriched population of Breast Cancer Stem Cells (BCSCs) from MCF7 cells with inducible expression of SrcDN. Induction of SrcDN inhibited self-renewal, and ...[more]

PMID: 32673341

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