A Transcriptional Signature and Common Gene Networks Link Cancer with Lipid Metabolism and Diverse Human Diseases

被引：301

作者：

Hirsch, Heather A. ^{[1
]}

Iliopoulos, Dimitrios ^{[1
]}

Joshi, Amita ^{[1
]}

Zhang, Yong ^{[2
]}

Jaeger, Savina A. ^{[3
]}

Bulyk, Martha ^{[3
,4
,5
]}

Tsichlis, Philip N. ^{[6
]}

Liu, X. Shirley ^{[2
]}

Struhl, Kevin ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA

[4] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[5] Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Boston, MA 02115 USA

[6] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA

来源：

CANCER CELL | 2010年 / 17卷 / 04期

基金：

美国国家卫生研究院;

关键词：

FATTY-ACID SYNTHASE; NF-KAPPA-B; BREAST-CANCER; EXPRESSION; INFLAMMATION; KINASE; CELLS; LIVER; ADENOCARCINOMA; IDENTIFICATION;

D O I：

10.1016/j.ccr.2010.01.022

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Transcriptional profiling of two isogenic models of transformation identifies a gene signature linking cancer with inflammatory and metabolic diseases. In accord with this common transcriptional program, many drugs used for treatment of diabetes and cardiovascular diseases inhibit transformation and tumor growth. Unexpectedly, lipid metabolism genes are important for transformation and are upregulated in cancer tissues. As in atherosclerosis, oxidized LDL and its receptor OLR1 activate the inflammatory pathway through NF-kappa B, leading to transformation. OLR1 is important for maintaining the transformed state in developmentally diverse cancer cell lines and for tumor growth, suggesting a molecular connection between cancer and atherosclerosis. We suggest that the interplay between this common transcriptional program and cell-type-specific factors gives rise to phenotypically disparate human diseases.

引用

页码：348 / 361

页数：14

共 42 条

[1] Diversity and Complexity in DNA Recognition by Transcription Factors [J].

Badis, Gwenael ;

Berger, Michael F. ;

Philippakis, Anthony A. ;

Talukder, Shaheynoor ;

Gehrke, Andrew R. ;

Jaeger, Savina A. ;

Chan, Esther T. ;

Metzler, Genita ;

Vedenko, Anastasia ;

Chen, Xiaoyu ;

Kuznetsov, Hanna ;

Wang, Chi-Fong ;

Coburn, David ;

Newburger, Daniel E. ;

Morris, Quaid ;

Hughes, Timothy R. ;

Bulyk, Martha L. .

SCIENCE, 2009, 324 (5935) :1720-1723

[2] Inflammation and cancer: back to Virchow? [J].

Balkwill, F ;

Mantovani, A .

LANCET, 2001, 357 (9255) :539-545

[3] An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors [J].

Ben-Porath, Ittai ;

Thomson, Matthew W. ;

Carey, Vincent J. ;

Ge, Ruping ;

Bell, George W. ;

Regev, Aviv ;

Weinberg, Robert A. .

NATURE GENETICS, 2008, 40 (05) :499-507

[4] Variation in homeodomain DNA binding revealed by high-resolution analysis of sequence preferences [J].

Berger, Michael F. ;

Badis, Gwenael ;

Gehrke, Andrew R. ;

Talukder, Shaheynoor ;

Philippakis, Anthony A. ;

Pena-Castillo, Lourdes ;

Alleyne, Trevis M. ;

Mnaimneh, Sanie ;

Botvinnik, Olga B. ;

Chan, Esther T. ;

Khalid, Faiqua ;

Zhang, Wen ;

Newburger, Daniel ;

Jaeger, Savina A. ;

Morris, Quaid D. ;

Bulyk, Martha L. ;

Hughes, Timothy R. .

CELL, 2008, 133 (07) :1266-1276

[5] Compact, universal DNA microarrays to comprehensively determine transcription-factor binding site specificities [J].

Berger, Michael F. ;

Philippakis, Anthony A. ;

Qureshi, Aaron M. ;

He, Fangxue S. ;

Estep, Preston W., III ;

Bulyk, Martha L. .

NATURE BIOTECHNOLOGY, 2006, 24 (11) :1429-1435

[6] Variations in DNA elucidate molecular networks that cause disease [J].

Chen, Yanqing ;

Zhu, Jun ;

Lum, Pek Yee ;

Yang, Xia ;

Pinto, Shirly ;

MacNeil, Douglas J. ;

Zhang, Chunsheng ;

Lamb, John ;

Edwards, Stephen ;

Sieberts, Solveig K. ;

Leonardson, Amy ;

Castellini, Lawrence W. ;

Wang, Susanna ;

Champy, Marie-France ;

Zhang, Bin ;

Emilsson, Valur ;

Doss, Sudheer ;

Ghazalpour, Anatole ;

Horvath, Steve ;

Drake, Thomas A. ;

Lusis, Aldons J. ;

Schadt, Eric E. .

NATURE, 2008, 452 (7186) :429-435

[7] Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data [J].

Dai, MH ;

Wang, PL ;

Boyd, AD ;

Kostov, G ;

Athey, B ;

Jones, EG ;

Bunney, WE ;

Myers, RM ;

Speed, TP ;

Akil, H ;

Watson, SJ ;

Meng, F .

NUCLEIC ACIDS RESEARCH, 2005, 33 (20) :e175.1-e175.9

[8] Inflammation in prostate carcinogenesis [J].

De Marzo, Angelo M. ;

Platz, Elizabeth A. ;

Sutcliffe, Siobhan ;

Xu, Jianfeng ;

Gronberg, Henrik ;

Drake, Charles G. ;

Nakai, Yasutomo ;

Isaacs, William B. ;

Nelson, William G. .

NATURE REVIEWS CANCER, 2007, 7 (04) :256-269

[9] Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures [J].

Debnath, J ;

Muthuswamy, SK ;

Brugge, JS .

METHODS, 2003, 30 (03) :256-268

[10] Gene expression and the biological phenotype of papillary thyroid carcinomas [J].

Delys, L. ;

Detours, V. ;

Franc, B. ;

Thomas, G. ;

Bogdanova, T. ;

Tronko, M. ;

Libert, F. ;

Dumont, J. E. ;

Maenhaut, C. .

ONCOGENE, 2007, 26 (57) :7894-7903

← 1 2 3 4 5 →