Your browser doesn't support javascript.
loading
Dickkopf-2 regulates the stem cell marker LGR5 in colorectal cancer via HNF4α1.
Shin, Jae Hun; Jeong, Jaekwang; Choi, Jungmin; Lim, Jaechul; Dinesh, Ravi K; Braverman, Jonathan; Hong, Jun Young; Maher, Stephen E; Amezcua Vesely, Maria C; Kim, WonJu; Koo, Ja-Hyun; Tang, Wenwen; Wu, Dianqing; Blackburn, Holly N; Xicola, Rosa M; Llor, Xavier; Yilmaz, Omer; Choi, Je-Min; Bothwell, Alfred L M.
Afiliación
  • Shin JH; Department of Immunobiology, Yale University School of Medicine, TAC 641D, PO Box 208011, 300 Cedar Street, New Haven, CT 06520-8011, USA.
  • Jeong J; Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Choi J; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Lim J; Department of Biomedical Sciences, Korea University College of Medicine, Seoul 02841, Korea.
  • Dinesh RK; Department of Immunobiology, Yale University School of Medicine, TAC 641D, PO Box 208011, 300 Cedar Street, New Haven, CT 06520-8011, USA.
  • Braverman J; Department of Immunobiology, Yale University School of Medicine, TAC 641D, PO Box 208011, 300 Cedar Street, New Haven, CT 06520-8011, USA.
  • Hong JY; The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
  • Maher SE; Department of Immunobiology, Yale University School of Medicine, TAC 641D, PO Box 208011, 300 Cedar Street, New Haven, CT 06520-8011, USA.
  • Amezcua Vesely MC; Department of Immunobiology, Yale University School of Medicine, TAC 641D, PO Box 208011, 300 Cedar Street, New Haven, CT 06520-8011, USA.
  • Kim W; Department of Immunobiology, Yale University School of Medicine, TAC 641D, PO Box 208011, 300 Cedar Street, New Haven, CT 06520-8011, USA.
  • Koo JH; Department of Life Science, College of Natural Science, Hanyang University, Seoul 04763, Republic of Korea.
  • Tang W; Department of Life Science, College of Natural Science, Hanyang University, Seoul 04763, Republic of Korea.
  • Wu D; Vascular Biology and Therapeutic Program and Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Blackburn HN; Vascular Biology and Therapeutic Program and Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Xicola RM; Department of Immunobiology, Yale University School of Medicine, TAC 641D, PO Box 208011, 300 Cedar Street, New Haven, CT 06520-8011, USA.
  • Llor X; Department of Surgery, Yale University School of Medicine, New Haven, CT 06520, USA.
  • Yilmaz O; Department of Medicine and Cancer Center, Yale University, New Haven, CT 06520, USA.
  • Choi JM; Department of Medicine and Cancer Center, Yale University, New Haven, CT 06520, USA.
  • Bothwell ALM; The David H. Koch Institute for Integrative Cancer Research at MIT, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
iScience ; 24(5): 102411, 2021 May 21.
Article en En | MEDLINE | ID: mdl-33997693
ABSTRACT
Enhanced stemness in colorectal cancer has been reported and it contributes to aggressive progression, but the underlying mechanisms remain unclear. Here we report a Wnt ligand, Dickkopf-2 (DKK2) is essential for developing colorectal cancer stemness. Genetic depletion of DKK2 in intestinal epithelial or stem cells reduced tumorigenesis and expression of the stem cell marker genes including LGR5 in a model of colitis-associated cancer. Sequential mutations in APC, KRAS, TP53, and SMAD4 genes in colonic organoids revealed a significant increase of DKK2 expression by APC knockout and further increased by additional KRAS and TP53 mutations. Moreover, DKK2 activates proto-oncogene tyrosine-protein kinse Src followed by increased LGR5 expressing cells in colorectal cancer through degradation of HNF4α1 protein. These findings suggest that DKK2 is required for colonic epithelial cells to enhance LGR5 expression during the progression of colorectal cancer.
Palabras clave
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: IScience Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: IScience Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos