【摘 要】
：
The cellular origin of gastric cancer remains elusive.Lgr5 is the first identified gastric stem cell marker.However, the role of Lgr5+ stem cells in driving
【机 构】
：
StateKeyLaboratoryofProteomics,GeneticLaboratoryofDevelopmentandDisease,InstituteofBiotechnology,Bei
论文部分内容阅读
The cellular origin of gastric cancer remains elusive.Lgr5 is the first identified gastric stem cell marker.However, the role of Lgr5+ stem cells in driving gastric carcinogenesis is not fully validated.Here, we used the inducible Cre-LoxP system to concurrently delete Smad4 and PTEN genes in mouse gastric Lgr5+ stem cells, and meanwhile marked mutant Lgr5+ cells and their progeny by Cre-reporter Rosa26tdTomato.Smad4 and PTEN double mutant Lgr5+ stem cells located at mouse gastric antrum and gastro-forestomach junction gave rise to rapid onset and progression from microadenoma, macroscopic adenoma to invasive adenocarcinoma within 3 months.Mutant Lgr5+ cells remained at the very base of benign adenoma,and unexpectedly, extensively occupied throughout the invasive lesions following malignant transition.Furthermore, transformed Lgr5+ cells exhibited proliferative activity.In human gastric cancer samples from TCGA database, the elevated LGR5 expression was observed in human gastric cancer occurred at antrum and gastro-esophageal junction.In addition, the concurrent deletion of SMAD4 and PTEN genes, as well as their reduced expression and the deregulated downstream pathways,were observed in human gastric cancer.Thus, we demonstrated that Lgr5+ gastric stem cells were cancer-initiating cells, and might act as cancer-propagating cells to contribute to malignant transition and invasion in gastric cancer.
其他文献
A critical clinical challenge in glioblastoma therapy is robust tumor growth and invasion driven by aberrant activation of oncogenic tyrosine receptor kinas
Adult mammalian cortex has long been regarded as "non-neurogenic".Recent studies have reported cortical neurogenesis after cerebral ischemia.However,whether
High glucose affects cell-cycle progression in many cells.The aim of this study was to explore whether high glucose-induced Erk1/2 activation regulates cell
How various ATP-dependent chromatin remodellers bind to nucleosomes to regulate transcription is not well defined in mammalian cells.Here, we present genome
Krüppel-like transcription factors (Klfs), each of which contains a CACCC-box binding domain, have been investigated in a variety of developmental processe
Alveoli collapse leading to respiratory failure is one of the major causes of death in newborn cloned calves.The present study focused on the expression pat
Hematopoietic stem and progenitor cells (HSPCs) have the capacity to self-renew and differentiate into all blood cell lineages, and thus sustain life-long h
The adult intestinal homeostasis is tightly controlled by proper proliferation and differentiation of intestinal stem cells.The JAK/STAT (Janus Kinase/Signal Tr
Highlights:1) Maternal Ascl1 functions as a repressor during mesendoderm pattern formation.2) Ascl1 recruits HDAC 1 to repress the transcriptional activity
In artificial insemination, semen quality is considered to be closely related to the pregnancy rate and ratio of embryo development into fetus.The aim of th