A luminal epithelial stem cell that is a cell of origin for prostate cancer

By Xi Wang, Marianna Kruithof-de Julio, Kyriakos D. Economides, D. Walker, Hailong Yu, M. Halili, Ya-Ping Hu, Sandy M. Price, C. Abate-Shen, M. Shen. Nature, 2009

764 citations recorded by the source corpus.

In epithelial tissues, the lineage relationship between normal progenitor cells and cell type(s) of origin for cancer has been poorly understood. Here we show that a known regulator of prostate epithelial differentiation, the homeobox gene Nkx3-1, marks a stem cell population that functions during prostate regeneration. Genetic lineage-marking demonstrates that rare luminal cells that express Nkx3-1 in the absence of testicular androgens (castration-resistant Nkx3-1-expressing cells, CARNs) are bipotential and can self-renew in vivo, and single-cell transplantation assays show that CARNs can reconstitute prostate ducts in renal grafts. Functional assays of Nkx3-1 mutant mice in serial prostate regeneration suggest that Nkx3-1 is required for stem cell maintenance. Furthermore, targeted deletion of the Pten tumour suppressor gene in CARNs results in rapid carcinoma formation after androgen-mediated regeneration. These observations indicate that CARNs represent a new luminal stem cell population that is an efficient target for oncogenic transformation in prostate cancer.

Subfields: Pulmonary and Respiratory Medicine, Surgery

View Paper: https://www.semanticscholar.org/paper/1f1fb4e9146dd457b9cf3d6200fe0cfe58088729

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Pulmonary and Respiratory Medicine

1. Hans Clevers
2. John Wongvipat
3. J. Rock
4. C. Sawyers
5. B. Hogan
6. S. Randell

In Surgery

1. Hans Clevers
2. B. Hogan

Citations in the corpus

• Identification of multipotent luminal progenitor cells in human prostate organoid cultures (2014, background): “1 expression postcastration can generate both lineages during regeneration of the prostate (Wang et al., 2009).”
• Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling (2010, background): “Support for the idea that a subset of lumenal cells can give rise to BCs after epithelial injury comes from recent transplantation and regeneration studies in the mouse prostate (Wang et al., 2009).”
• Genetics and biology of prostate cancer (2018, methodology): “The genesis issues may be addressed in part with minimal dosing of OHT to activate Cre-ER recombinase in fewer cells, as shown elsewhere (Boutin et al. 2017), or prostate injection of lentiviral-Cre with defined low multiplicity of infection (MOI) in mice harboring conditional alleles (Cho et al. 20”
• Molecular genetics of prostate cancer: new prospects for old challenges. (2010, background): “Furthermore, recent studies have identified a rare luminal population of CARNs in the regressed prostate epithelium that displays stem cell properties during prostate regeneration (X Wang et al. 2009).”