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Mist1 Expressing Gastric Stem Cells Maintain the Normal and Neoplastic Gastric Epithelium and Are Supported by a Perivascular Stem Cell Niche
- Source :
- Elsevier, Paediatrics Publications
- Publication Year :
- 2015
- Publisher :
- Elsevier, 2015.
-
Abstract
- The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1⁺ stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse-type cancer with the loss of E-cadherin. Diffuse-type cancer development is dependent on inflammation mediated by Cxcl12⁺ endothelial cells and Cxcr4⁺ gastric innate lymphoid cells (ILCs). These cells form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in the E-cadherin-depleted cells. Targeting Cxcr4, ILCs, or Wnt5a inhibits diffuse-type gastric carcinogenesis, providing targets within the neoplastic gastric stem cell niche.<br />National Institutes of Health (U.S.) (Grants 54CA126513, R01CA093405, R01CA120979, and R01DK052778)
- Subjects :
- Male
rho GTP-Binding Proteins
Cancer Research
Time Factors
Cell Communication
CXCR4
Mice
Gastric glands
Basic Helix-Loop-Helix Transcription Factors
Tumor Microenvironment
Anoikis
Lymphocytes
Stem Cell Niche
Enterochromaffin-like cell
Wnt Signaling Pathway
Cellular Senescence
Bone Marrow Transplantation
Cadherins
Endothelial stem cell
Cell Transformation, Neoplastic
medicine.anatomical_structure
Oncology
Neoplastic Stem Cells
Stem cell
Signal Transduction
Adult stem cell
Receptors, CXCR4
Antineoplastic Agents
Mice, Transgenic
Biology
Wnt-5a Protein
Stomach Neoplasms
Cancer stem cell
Cell Line, Tumor
medicine
Animals
Humans
Cell Lineage
Endothelial Cells
Epithelial Cells
Cell Biology
Chemokine CXCL12
digestive system diseases
Wnt Proteins
body regions
Gastric Mucosa
Immunology
Cancer research
rhoA GTP-Binding Protein
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Elsevier, Paediatrics Publications
- Accession number :
- edsair.doi.dedup.....fc4306c010f54e0c928b60e731a2a9e7