TGFβ induces the formation of tumour-initiating cells in claudinlow breast cancer

被引：90

作者：

Bruna, Alejandra ^{[1
,2
]}

Greenwood, Wendy ^{[1
,2
]}

Le Quesne, John ^{[1
,2
]}

Teschendorff, Andrew ^{[3
]}

Miranda-Saavedra, Diego ^{[4
]}

Rueda, Oscar M. ^{[1
,2
]}

Sandoval, Jose L. ^{[1
,2
]}

Vidakovic, Ana Tufegdzic ^{[1
,2
]}

Saadi, Amel ^{[1
,2
]}

Pharoah, Paul ^{[5
,6
,7
,8
]}

Stingl, John ^{[1
,2
]}

Caldas, Carlos ^{[1
,2
,6
,7
,8
]}

机构：

[1] Canc Res UK, Li Ka Shing Ctr, Cambridge Res Inst, Cambridge CB2 0RE, England

[2] Univ Cambridge, Li Ka Shing Ctr, Dept Oncol, Cambridge CB2 0RE, England

[3] UCL, UCL Canc Inst, Med Genom Grp, London WC1E 6BT, England

[4] Osaka Univ, World Premier Int WPI Immunol Frontier Res Ctr IF, Bioinformat & Genom Lab, Suita, Osaka 5650871, Japan

[5] Univ Cambridge, Strangeways Res Labs, Dept Oncol, Cambridge CB1 8RN, England

[6] Univ Cambridge, Addenbrookes Hosp, Cambridge Breast Unit, Hosp NHS Fdn Trust, Cambridge CB2 0QQ, England

[7] NIHR Cambridge Biomed Res, Cambridge CB2 0QQ, England

[8] Cambridge Expt Canc Med Ctr, Cambridge CB2 0RE, England

来源：

NATURE COMMUNICATIONS | 2012年 / 3卷

关键词：

GROWTH-FACTOR-BETA; TO-MESENCHYMAL TRANSITION; EPITHELIAL STEM-CELLS; PROSPECTIVE IDENTIFICATION; MOLECULAR HETEROGENEITY; TRANSCRIPTION FACTORS; PROGENITOR-CELL; IN-VITRO; EXPRESSION; GENE;

D O I：

10.1038/ncomms2039

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The role of transforming growth factor-beta (TGF beta) in the progression of different molecular subtypes of breast cancer has not been clarified. Here we show that TGF beta increases breast tumour-initiating cell (BTIC) numbers but only in claudin(low) breast cancer cell lines by orchestrating a specific gene signature enriched in stem cell processes that predicts worse clinical outcome in breast cancer patients. NEDD9, a member of the Cas family of integrin scaffold proteins, is necessary to mediate these TGF beta-specific effects through a positive feedback loop that integrates TGF beta/Smad and Rho-actin-SRF-dependent signals. In normal human mammary epithelium, TGF beta induces progenitor activity only in the basal/stem cell compartment, where claudin(low) cancers are presumed to arise. These data show opposing responses to TGF beta in both breast malignant cell subtypes and normal mammary epithelial cell subpopulations and suggest therapeutic strategies for a subset of human breast cancers.

引用

页数：12

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