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A recellularized human colon model identifies cancer driver genes.

Publication ,  Journal Article
Chen, HJ; Wei, Z; Sun, J; Bhattacharya, A; Savage, DJ; Serda, R; Mackeyev, Y; Curley, SA; Bu, P; Wang, L; Chen, S; Cohen-Gould, L; Huang, E ...
Published in: Nat Biotechnol
August 2016

Refined cancer models are needed to bridge the gaps between cell line, animal and clinical research. Here we describe the engineering of an organotypic colon cancer model by recellularization of a native human matrix that contains cell-populated mucosa and an intact muscularis mucosa layer. This ex vivo system recapitulates the pathophysiological progression from APC-mutant neoplasia to submucosal invasive tumor. We used it to perform a Sleeping Beauty transposon mutagenesis screen to identify genes that cooperate with mutant APC in driving invasive neoplasia. We identified 38 candidate invasion-driver genes, 17 of which, including TCF7L2, TWIST2, MSH2, DCC, EPHB1 and EPHB2 have been previously implicated in colorectal cancer progression. Six invasion-driver genes that have not, to our knowledge, been previously described were validated in vitro using cell proliferation, migration and invasion assays and ex vivo using recellularized human colon. These results demonstrate the utility of our organoid model for studying cancer biology.

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Published In

Nat Biotechnol

DOI

EISSN

1546-1696

Publication Date

August 2016

Volume

34

Issue

8

Start / End Page

845 / 851

Location

United States

Related Subject Headings

  • Tissue Engineering
  • Organogenesis
  • Neoplasm Proteins
  • Humans
  • Genes, Neoplasm
  • Gene Expression Profiling
  • Colonic Neoplasms
  • Colon
  • Cells, Cultured
  • Cell-Free System
 

Citation

APA
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ICMJE
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Chen, H. J., Wei, Z., Sun, J., Bhattacharya, A., Savage, D. J., Serda, R., … Shuler, M. L. (2016). A recellularized human colon model identifies cancer driver genes. Nat Biotechnol, 34(8), 845–851. https://doi.org/10.1038/nbt.3586
Chen, Huanhuan Joyce, Zhubo Wei, Jian Sun, Asmita Bhattacharya, David J. Savage, Rita Serda, Yuri Mackeyev, et al. “A recellularized human colon model identifies cancer driver genes.Nat Biotechnol 34, no. 8 (August 2016): 845–51. https://doi.org/10.1038/nbt.3586.
Chen HJ, Wei Z, Sun J, Bhattacharya A, Savage DJ, Serda R, et al. A recellularized human colon model identifies cancer driver genes. Nat Biotechnol. 2016 Aug;34(8):845–51.
Chen, Huanhuan Joyce, et al. “A recellularized human colon model identifies cancer driver genes.Nat Biotechnol, vol. 34, no. 8, Aug. 2016, pp. 845–51. Pubmed, doi:10.1038/nbt.3586.
Chen HJ, Wei Z, Sun J, Bhattacharya A, Savage DJ, Serda R, Mackeyev Y, Curley SA, Bu P, Wang L, Chen S, Cohen-Gould L, Huang E, Shen X, Lipkin SM, Copeland NG, Jenkins NA, Shuler ML. A recellularized human colon model identifies cancer driver genes. Nat Biotechnol. 2016 Aug;34(8):845–851.

Published In

Nat Biotechnol

DOI

EISSN

1546-1696

Publication Date

August 2016

Volume

34

Issue

8

Start / End Page

845 / 851

Location

United States

Related Subject Headings

  • Tissue Engineering
  • Organogenesis
  • Neoplasm Proteins
  • Humans
  • Genes, Neoplasm
  • Gene Expression Profiling
  • Colonic Neoplasms
  • Colon
  • Cells, Cultured
  • Cell-Free System