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Epigenetic basis of oncogenic-Kras-mediated epithelial-cellular proliferation and plasticity.

Publication ,  Journal Article
Kadur Lakshminarasimha Murthy, P; Xi, R; Arguijo, D; Everitt, JI; Kocak, DD; Kobayashi, Y; Bozec, A; Vicent, S; Ding, S; Crawford, GE; Hsu, D ...
Published in: Dev Cell
February 7, 2022

Oncogenic Kras induces a hyper-proliferative state that permits cells to progress to neoplasms in diverse epithelial tissues. Depending on the cell of origin, this also involves lineage transformation. Although a multitude of downstream factors have been implicated in these processes, the precise chronology of molecular events controlling them remains elusive. Using mouse models, primary human tissues, and cell lines, we show that, in Kras-mutant alveolar type II cells (AEC2), FOSL1-based AP-1 factor guides the mSWI/SNF complex to increase chromatin accessibility at genomic loci controlling the expression of genes necessary for neoplastic transformation. We identified two orthogonal processes in Kras-mutant distal airway club cells. The first promoted their transdifferentiation into an AEC2-like state through NKX2.1, and the second controlled oncogenic transformation through the AP-1 complex. Our results suggest that neoplasms retain an epigenetic memory of their cell of origin through cell-type-specific transcription factors. Our analysis showed that a cross-tissue-conserved AP-1-dependent chromatin remodeling program regulates carcinogenesis.

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Published In

Dev Cell

DOI

EISSN

1878-1551

Publication Date

February 7, 2022

Volume

57

Issue

3

Start / End Page

310 / 328.e9

Location

United States

Related Subject Headings

  • Transcription Factor AP-1
  • Proto-Oncogene Proteins p21(ras)
  • Proto-Oncogene Proteins c-fos
  • Organ Specificity
  • Oncogenes
  • Nucleosomes
  • Neoplasms
  • Mutation
  • Mutant Proteins
  • Mice, SCID
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kadur Lakshminarasimha Murthy, P., Xi, R., Arguijo, D., Everitt, J. I., Kocak, D. D., Kobayashi, Y., … Shen, X. (2022). Epigenetic basis of oncogenic-Kras-mediated epithelial-cellular proliferation and plasticity. Dev Cell, 57(3), 310-328.e9. https://doi.org/10.1016/j.devcel.2022.01.006
Kadur Lakshminarasimha Murthy, Preetish, Rui Xi, Diana Arguijo, Jeffrey I. Everitt, Dewran D. Kocak, Yoshihiko Kobayashi, Aline Bozec, et al. “Epigenetic basis of oncogenic-Kras-mediated epithelial-cellular proliferation and plasticity.Dev Cell 57, no. 3 (February 7, 2022): 310-328.e9. https://doi.org/10.1016/j.devcel.2022.01.006.
Kadur Lakshminarasimha Murthy P, Xi R, Arguijo D, Everitt JI, Kocak DD, Kobayashi Y, et al. Epigenetic basis of oncogenic-Kras-mediated epithelial-cellular proliferation and plasticity. Dev Cell. 2022 Feb 7;57(3):310-328.e9.
Kadur Lakshminarasimha Murthy, Preetish, et al. “Epigenetic basis of oncogenic-Kras-mediated epithelial-cellular proliferation and plasticity.Dev Cell, vol. 57, no. 3, Feb. 2022, pp. 310-328.e9. Pubmed, doi:10.1016/j.devcel.2022.01.006.
Kadur Lakshminarasimha Murthy P, Xi R, Arguijo D, Everitt JI, Kocak DD, Kobayashi Y, Bozec A, Vicent S, Ding S, Crawford GE, Hsu D, Tata PR, Reddy T, Shen X. Epigenetic basis of oncogenic-Kras-mediated epithelial-cellular proliferation and plasticity. Dev Cell. 2022 Feb 7;57(3):310-328.e9.
Journal cover image

Published In

Dev Cell

DOI

EISSN

1878-1551

Publication Date

February 7, 2022

Volume

57

Issue

3

Start / End Page

310 / 328.e9

Location

United States

Related Subject Headings

  • Transcription Factor AP-1
  • Proto-Oncogene Proteins p21(ras)
  • Proto-Oncogene Proteins c-fos
  • Organ Specificity
  • Oncogenes
  • Nucleosomes
  • Neoplasms
  • Mutation
  • Mutant Proteins
  • Mice, SCID