Tgfbr2 inactivation facilitates cellular plasticity and development of Pten-null prostate cancer

Wei Zhao, Qingyuan Zhu, Peng Tan, Adebusola Ajibade, Teng Long, Wenyong Long, Qingtian Li, Pinghua Liu, Bo Ning, Helen Y. Wang, Rong Fu Wang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Mutations in tumors can create a state of increased cellular plasticity that promotes resistance to treatment. Thus, there is an urgent need to develop novel strategies for identifying key factors that regulate cellular plasticity in order to combat resistance to chemotherapy and radiation treatment. Here we report that prostate epithelial cell reprogramming could be exploited to identify key factors required for promoting prostate cancer tumorigenesis and cellular plasticity. Deletion of phosphatase and tensin homolog (Pten) and transforming growth factor-beta receptor type 2 (Tgfbr2) may increase prostate epithelial cell reprogramming efficiency in vitro and cause rapid tumor development and early mortality in vivo. Tgfbr2 ablation abolished TGF-β signaling but increased the bone morphogenetic protein (BMP) signaling pathway through the negative regulator Tmeff1. Furthermore, increased BMP signaling promotes expression of the tumor marker genes ID1, Oct4, Nanog, and Sox2; ID1/STAT3/NANOG expression was inversely correlated with patient survival. Thus, our findings provide information about the molecular mechanisms by which BMP signaling pathways render stemness capacity to prostate tumor cells.

Original languageEnglish (US)
Pages (from-to)316-330
Number of pages15
JournalJournal of Molecular Cell Biology
Volume10
Issue number4
DOIs
StatePublished - Aug 1 2018
Externally publishedYes

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Transforming Growth Factor beta Receptors
Bone Morphogenetic Proteins
Phosphoric Monoester Hydrolases
Prostate
Prostatic Neoplasms
Epithelial Cells
Neoplasms
Tumor Biomarkers
Carcinogenesis
Radiation
Drug Therapy
Mutation
Survival
Mortality
Therapeutics
Genes
Tensins
Cell Plasticity
Cellular Reprogramming

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Tgfbr2 inactivation facilitates cellular plasticity and development of Pten-null prostate cancer. / Zhao, Wei; Zhu, Qingyuan; Tan, Peng; Ajibade, Adebusola; Long, Teng; Long, Wenyong; Li, Qingtian; Liu, Pinghua; Ning, Bo; Wang, Helen Y.; Wang, Rong Fu.

In: Journal of Molecular Cell Biology, Vol. 10, No. 4, 01.08.2018, p. 316-330.

Research output: Contribution to journalArticle

Zhao, W, Zhu, Q, Tan, P, Ajibade, A, Long, T, Long, W, Li, Q, Liu, P, Ning, B, Wang, HY & Wang, RF 2018, 'Tgfbr2 inactivation facilitates cellular plasticity and development of Pten-null prostate cancer', Journal of Molecular Cell Biology, vol. 10, no. 4, pp. 316-330. https://doi.org/10.1093/jmcb/mjx052
Zhao, Wei ; Zhu, Qingyuan ; Tan, Peng ; Ajibade, Adebusola ; Long, Teng ; Long, Wenyong ; Li, Qingtian ; Liu, Pinghua ; Ning, Bo ; Wang, Helen Y. ; Wang, Rong Fu. / Tgfbr2 inactivation facilitates cellular plasticity and development of Pten-null prostate cancer. In: Journal of Molecular Cell Biology. 2018 ; Vol. 10, No. 4. pp. 316-330.
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AU - Li, Qingtian

AU - Liu, Pinghua

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