Targeted BMI1 inhibition impairs tumor growth in lung adenocarcinomas with low CEBPα expression

Author:

Yong Kol Jia1,Basseres Daniela S.2345,Welner Robert S.3456,Zhang Wen Cai347,Yang Henry1,Yan Benedict8,Alberich-Jorda Meritxell3459,Zhang Junyan345,de Figueiredo-Pontes Lorena Lobo34510,Battelli Chiara34,Hetherington Christopher J.345,Ye Min345,Zhang Hong345,Maroni Giorgia11,O’Brien Karen345,Magli Maria Cristina11,Borczuk Alain C.12,Varticovski Lyuba13,Kocher Olivier34,Zhang Pu345,Moon Young-Choon14,Sydorenko Nadiya14,Cao Liangxian14,Davis Thomas W.14,Thakkar Bhavin M.1,Soo Ross A.115,Iwama Atsushi16,Lim Bing347,Halmos Balazs17,Neuberg Donna18,Tenen Daniel G.145,Levantini Elena34511

Affiliation:

1. Cancer Science Institute, National University of Singapore, Singapore 117599, Singapore.

2. Biochemistry Department, Chemistry Institute, University of São Paulo, São Paulo 05508, Brazil.

3. Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.

4. Harvard Medical School, Boston, MA 02215, USA.

5. Harvard Stem Cell Institute, Boston, MA 02215, USA.

6. Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA.

7. Stem Cell and Developmental Biology, Genome Institute of Singapore, Singapore 138672, Singapore.

8. Department of Pathology and Laboratory Medicine, KK Women’s and Children’s Hospital, Singapore 119074, Singapore.

9. Institute of Molecular Genetics of the ASCR, Prague 14200, Czech Republic.

10. Hematology Division, Department of Internal Medicine, Ribeirao Preto Medical School, University of São Paulo, São Paulo 14020, Brazil.

11. Institute of Biomedical Technologies, National Research Council (CNR), Pisa 56124, Italy.

12. Department of Pathology, Weill Cornell University Medical Center, New York, NY 10065, USA.

13. Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD 20817, USA.

14. PTC Therapeutics, 100 Corporate Court, South Plainfield, NJ 07080, USA.

15. Department of Haematology-Oncology, University of Western Australia, Crawley, Western Australia 6009, Australia.

16. Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.

17. Division of Hematology/Oncology, Montefiore Hospital, Bronx, NY 10461, USA.

18. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Abstract

In lung cancers with low expression of C/EBPα, BMI1 expression correlates with worse prognosis but can be targeted with a drug.

Funder

National Cancer Institute

National University Cancer Institute of Singapore

Yong Loo Lin Trust

Singapore Translational Research

National Research Foundation of Singapore

Singapore Ministry of Education

FAMRI (Flight Attendant Medical Research Institute)

YCSA (Young Clinical Scientist Award)

FAMRI CIA (Clinical Innovator Awards)

FAMRI YCSA

Doctors Cancer Foundation Award

IASLC (International Association for the Study of Lung Cancer) Award

MIUR (Ministry of Education, University and Research)

MSMT Navrat

NCI

Agency for Science, Technology and Research (A*STAR), Singapore

National Medical Research Council of Singapore

Dana-Farber/Harvard Cancer Center

Publisher

American Association for the Advancement of Science (AAAS)

Subject

General Medicine

Reference50 articles.

1. Cancer statistics, 2012

2. Epigenetic Modulation of Tumor Suppressor CCAAT/Enhancer Binding Protein α Activity in Lung Cancer

3. Genome-wide allelotyping of lung cancer identifies new regions of allelic loss, differences between small cell lung cancer and non-small cell lung cancer, and loci clustering;Girard L.;Cancer Res.,2000

4. Dysregulation of the C/EBPα Differentiation Pathway in Human Cancer

5. Dominant-negative mutations of CEBPA, encoding CCAAT/enhancer binding protein-α (C/EBPα), in acute myeloid leukemia

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