LGR5 promotes the proliferation of colorectal cancer cells via the Wnt/β-catenin signaling pathway

Lin, Yun‐Tien; Wu, Tingyu; Yao, Qianqian; Zi, Shuming; Cui, Long; Yang, Ming; Li, Jinming

doi:10.3892/ol.2015.3144

Cited by 24 publications

(20 citation statements)

References 40 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…LGR5 was an established cancer stem cell marker and could promote the proliferation of CRC cells via the Wnt/b-catenin signaling pathway, which was a critical pathway in the process of tumor initiation and growth (Lin et al, 2015). CLDN1, a member of the claudin family, was an integral membrane protein and a component of tight junction strands.…”

Section: Identification Of Genes Related To Clinicopathological Charamentioning

confidence: 99%

Identification of Genes Related to Clinicopathological Characteristics and Prognosis of Patients with Colorectal Cancer

Gao

Yang

2020

DNA and Cell Biology

View full text Add to dashboard Cite

The aim of this study was to identify genes with clinical significance in colorectal cancer (CRC). Gene expression profiles of 585 CRC tissues and 61 normal colorectal tissues from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases were used to identify differentially expressed genes (DEGs) between CRC and normal colorectal tissues. DAVID and KOBAS tools were used to explore Gene Ontology (GO) and KEGG pathways enriched by DEGs, respectively. In addition, TCGA data sets were also used to identify prognostic factors and develop a prognostic prediction model for CRC. A total of 353 DEGs including 117 upregulated and 236 downregulated genes in CRC were identified based on GSE32323 data set. These DEGs were significantly enriched in the biological process related to the regulation of cell proliferation and 50 signaling pathways, such as ''TGF-beta signaling pathway,'' ''Wnt signaling pathway,'' and ''Jak-STAT signaling pathway.'' GCG, ADH1B, SLC4A4, ZG16, and CLCA4 were the top five downregulated in CRC. FOXQ1, LGR5, CLDN1, KRT23, and DPEP1 were the top five upregulated in CRC. KRT23 expression could affect tumor stage and regional lymph node metastasis in CRC patients. FOXQ1 expression could affect tumor distant metastasis in CRC patients. Survival analysis indicated that SLC4A4 expression was associated with the prognosis of CRC patients. Prognostic prediction model developed based on age, tumor stage, and SLC4A4 expression exhibited an efficient performance in predicting 1-, 3-, and 5-year overall survival of CRC patients. In conclusion, the current study identified several genes and pathways related to CRC, which provided new insight in understanding molecular mechanism of tumorigenesis and development of CRC.

show abstract

Section: Identification Of Genes Related To Clinicopathological Charamentioning

confidence: 99%

Identification of Genes Related to Clinicopathological Characteristics and Prognosis of Patients with Colorectal Cancer

Gao

Yang

2020

DNA and Cell Biology

View full text Add to dashboard Cite

show abstract

“…Wnt/β-catenin signaling works as the primary driving force behind these processes in the intestinal crypts 32 . Lgr5 is a marker of intestinal stem cells with a well-de ned function in the promotion of Wnt/β-catenin signaling 33 via modulation of the expression of adenomatous polyposis coli (APC) protein and β-catenin 34 .…”

Section: Discussionmentioning

confidence: 99%

Unveiling role of Sphingosine-1-phosphate receptor 2 as a brake of epithelial stem cell proliferation and a tumor suppressor in colorectal cancer

Petti

Rizzo

Rubbino

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundSphingosine-1-phosphate receptor 2 (S1PR2) mediates pleiotropic functions encompassing cell proliferation, survival, and migration, which become collectively de-regulated in cancer. Information onto whether S1PR2 participates in colorectal carcinogenesis/cancer is scanty, and we set out to fill the gap.MethodsWe screened expression changes of S1PR2 in human CRC and matched normal mucosa specimens [N = 76]. We compared CRC arising in inflammation-driven and genetically engineered models in wild-type (S1PR2+/+) and S1PR2 deficient (S1PR2−/−) mice. We reconstituted S1PR2 expression in RKO cells and assessed their growth in xenografts. Functionally, we mimicked ablation of S1PR2 in normal mucosa by treating S1PR2+/+ organoids with JTE013, and characterized intestinal epithelial stem cells isolated from S1PR2−/−Lgr5-EGFP- mice.ResultsS1PR2 expression was lost in 33% of CRC; in 55%, it was significantly decreased, only 12% retaining expression comparable to normal mucosa. Both colitis-induced and genetic Apc+/min mouse models of CRC showed a higher incidence in size and number of carcinomas and/or high-grade adenomas, with increased cell proliferation in S1PR2−/− mice compared to S1PR2+/+ controls. Loss of S1PR2 impaired mucosal regeneration, ultimately promoting the expansion of intestinal stem cells. Whereas its overexpression attenuated cell cycle progression, it reduced the phosphorylation of AKT and augmented the levels of PTEN.ConclusionsIn normal colonic crypts, S1PR2 gains expression along with intestinal epithelial cells differentiation, but not in intestinal stem cells, and contrasts intestinal tumorigenesis by promoting epithelial differentiation, preventing the expansion of stem cells and braking their malignant transformation. Targeting of S1PR2 may be of therapeutic benefit for CRC expressing high Lgr5.

show abstract

“…Wnt/β-catenin signaling works as the primary driving force behind these processes in the intestinal crypts (34). Lgr5 is a marker of intestinal stem cells with a well-de ned function in the promotion of Wnt/β-catenin signalling (35) via modulation of the expression of adenomatous polyposis coli (APC) protein and β-catenin (36).…”

Section: Discussionmentioning

confidence: 99%

Unveiling role of Sphingosine-1-phosphate receptor 2 as a brake of epithelial stem cell proliferation and a tumor suppressor in colorectal cancer

Petti

Rizzo

Rubbino

et al. 2020

Preprint

View full text Add to dashboard Cite

Background. Sphingosine-1-phosphate receptor 2 (S1PR2) mediates pleiotropic functions encompassing cell proliferation, survival, and migration, which become collectively de-regulated in cancer. Information on whether S1PR2 participates in colorectal carcinogenesis/cancer is scanty, and we set out to fill the gap.Methods. We screened expression changes of S1PR2 in human CRC and matched normal mucosa specimens [N=76]. We compared CRC arising in inflammation-driven and genetically engineered models in wild-type (S1PR2+/+) and S1PR2 deficient (S1PR2-/-) mice. We reconstituted S1PR2 expression in RKO cells and assessed their growth in xenografts. Functionally, we mimicked the ablation of S1PR2 in normal mucosa by treating S1PR2+/+ organoids with JTE013 and characterized intestinal epithelial stem cells isolated from S1PR2-/-Lgr5-EGFP- mice.Results. S1PR2 expression was lost in 33% of CRC; in 55%, it was significantly decreased, only 12% retaining expression comparable to normal mucosa. Both colitis-induced and genetic Apc+/min mouse models of CRC showed a higher incidence in size and number of carcinomas and/or high-grade adenomas, with increased cell proliferation in S1PR2-/- mice compared to S1PR2+/+ controls. Loss of S1PR2 impaired mucosal regeneration, ultimately promoting the expansion of intestinal stem cells. Whereas its overexpression attenuated cell cycle progression, it reduced the phosphorylation of AKT and augmented the levels of PTEN.Conclusions. In normal colonic crypts, S1PR2 gains expression along with intestinal epithelial cells differentiation, but not in intestinal stem cells, and contrasts intestinal tumorigenesis by promoting epithelial differentiation, preventing the expansion of stem cells and braking their malignant transformation. Targeting of S1PR2 may be of therapeutic benefit for CRC expressing high Lgr5.

show abstract

LGR5 promotes the proliferation of colorectal cancer cells via the Wnt/β-catenin signaling pathway

Cited by 24 publications

References 40 publications

Identification of Genes Related to Clinicopathological Characteristics and Prognosis of Patients with Colorectal Cancer

Identification of Genes Related to Clinicopathological Characteristics and Prognosis of Patients with Colorectal Cancer

Unveiling role of Sphingosine-1-phosphate receptor 2 as a brake of epithelial stem cell proliferation and a tumor suppressor in colorectal cancer

Unveiling role of Sphingosine-1-phosphate receptor 2 as a brake of epithelial stem cell proliferation and a tumor suppressor in colorectal cancer

Contact Info

Product

Resources

About