Abstract 5201: Distinctive distribution of expression of Lgr5, an intestinal stem cell marker, during each stage of colorectal tumorigenesis

Takeda, Kouichi; Kinoshita, Ichiro; Shimizu, Yasushi; Matsuno, Yoshihiro; Shichinohe, Toshiaki; Dosaka‐Akita, Hirotoshi

doi:10.1158/1538-7445.am2011-5201

Cited by 39 publications

(70 citation statements)

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“…4d), mimicking the LGR5 expression pattern in healthy colon tissue. In contrast, LS174T cells that expressed GalNAc-T6 had a high number of LGR5-positive cells in the upper layers of the colonies, with increasing staining intensity at the luminal surface, similar to the expression pattern of LGR5 in human colon cancer (73). This may indicate that GalNAc-T6 expression induces a cancer-like LGR5 expression pattern in these colonies (Fig.…”

Section: Cancer-associated Expression Of Human Pp-galnac-t6mentioning

confidence: 71%

De novo expression of human polypeptide N-acetylgalactosaminyltransferase 6 (GalNAc-T6) in colon adenocarcinoma inhibits the differentiation of colonic epithelium

Lavrsen

Dabelsteen

Vakhrushev

et al. 2018

Journal of Biological Chemistry

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Edited by Eric R. FearonAberrant expression of O-glycans is a hallmark of epithelial cancers. Mucin-type O-glycosylation is initiated by a large family of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) that target different proteins and are differentially expressed in cells and organs. Here, we investigated the expression patterns of all of the GalNAc-Ts in colon cancer by analyzing transcriptomic data. We found that GalNAc-T6 was highly up-regulated in colon adenocarcinomas but absent in normal-appearing adjacent colon tissue. These results were verified by immunohistochemistry, suggesting that GalNAc-T6 plays a role in colon carcinogenesis. To investigate the function of GalNAc-T6 in colon cancer, we used precise gene targeting to produce isogenic colon cancer cell lines with a knockout/rescue system for GALNT6. GalNAc-T6 expression was associated with a cancer-like, dysplastic growth pattern, whereas GALNT6 knockout cells showed a more normal differentiation pattern, reduced proliferation, normalized cell-cell adhesion, and formation of crypts in tissue cultures. O-Glycoproteomic analysis of the engineered cell lines identified a small set of GalNAc-T6 -specific targets, suggesting that this isoform has unique cellular functions. In support of this notion, the genetically and functionally closely related GalNAc-T3 homolog did not show compensatory functionality for effects observed for GalNAc-T6. Taken together, these data strongly suggest that aberrant GalNAc-T6 expression and site-specific glycosylation is involved in oncogenic transformation.

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Section: Cancer-associated Expression Of Human Pp-galnac-t6mentioning

confidence: 71%

De novo expression of human polypeptide N-acetylgalactosaminyltransferase 6 (GalNAc-T6) in colon adenocarcinoma inhibits the differentiation of colonic epithelium

Lavrsen

Dabelsteen

Vakhrushev

et al. 2018

Journal of Biological Chemistry

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“…Many studies have found that LGR5 expression is higher in tumor tissues than in adjacent nontumor tissues and promotes cell proliferation and tumor formation [21,37,38]. However, another study suggested that LGR5 was a negative regulator of tumorigenicity in colorectal carcinomas [39].…”

Section: Discussionmentioning

confidence: 99%

LGR5 Promotes Breast Cancer Progression and Maintains Stem-Like Cells Through Activation of Wnt/β-Catenin Signaling

et al. 2015

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The cancer stem cell (CSC) hypothesis suggests that a subset of cancer cells possesses stem cell properties and is crucial in tumor initiation, metastasis, and drug resistance. To determine the mechanism of CSCs in breast cancer, we focused on LGR5, a marker of adult stem cells that potentially serves as a functional factor in CSCs.LGR5 overexpression was detected in breast cancer and significantly associated with breast cancer recurrence and poor outcome.LGR5 promoted cell mobility, tumor formation, and epithelial-mesenchymal transition in breast cancer cells by activating Wnt/b-catenin signaling. In addition, LGR5 was more highly expressed in tumorspheres and increased the stemness of breast cancer cells. Compared with LGR5 lowexpression (LGR5 low ) cells, LGR5 high cells exhibited CSC/tumor-initiating cell-like properties, including the formation of self-renewing spheres and high tumorigenicity. Importantly, our studies indicate that LGR5 activation of Wnt/b-catenin signaling is a possible mechanism to regulate breast CSC/tumor-initiating cell renewal. These findings indicate that LGR5 not only participates in carcinogenesis but also maintained stemness by activating Wnt/b-catenin signaling in breast cancer. STEM CELLS 2015;33:2913-2924 SIGNIFICANCE STATEMENTThe cancer stem cell hypothesis suggests that a subset of cancer cells possess stem cell properties and are crucial in tumor initiation, metastasis and drug resistance. To determine the mechanism of cancer stem cell in breast cancer, we focused our sight on LGR5, a marker for adult stem cells.LGR5 is overexpressed in breast cancer and is associated with poor outcomes. LGR5 promotes cell mobility, tumor formation and Epithelial-Mesenchymal Transition in breast cancer cells by activating Wnt/b-catenin signaling. Importantly, LGR5 activation of Wnt/b-catenin signaling is a possible mechanism to regulate breast cancer stem cell renewal. These findings indicate that LGR5 not only participates in carcinogenesis but also maintained stemness by activating Wnt/b-catenin signaling in breast cancer.

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“…Colorectal CSCs (CCSC) have been distinguished using CD44 or CD133 either alone (8)(9)(10), or combined with other markers, such as EpCAM, CD166, CD29, CD24, LGR5 and aldehyde dehydrogenase 1 (ALDH1; refs. [11][12][13]. Previous studies by ourselves and other authors have shown that as few as 100 CD44 þ cancer cells isolated from patients were able to develop into a heterogeneous tumor, and that spheroids derived from a single CD44 þ cancer cell could recapitulate the heterogeneous hierarchy of tumor cells (8,14).…”

Section: Introductionmentioning

confidence: 92%

CD44-Positive Cancer Stem Cells Expressing Cellular Prion Protein Contribute to Metastatic Capacity in Colorectal Cancer

Rao

Wang

et al. 2013

Cancer Research

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Cancer stem cells are implicated in tumor progression, metastasis, and recurrence, although the exact mechanisms remain poorly understood. Here, we show that the expression of cellular prion protein (PrPc, PRNP) is positively correlated with an increased risk of metastasis in colorectal cancer. PrPc defines a subpopulation of CD44-positive cancer stem cells that contributes to metastatic capacity.

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Abstract 5201: Distinctive distribution of expression of Lgr5, an intestinal stem cell marker, during each stage of colorectal tumorigenesis

Cited by 39 publications

References 0 publications

De novo expression of human polypeptide N-acetylgalactosaminyltransferase 6 (GalNAc-T6) in colon adenocarcinoma inhibits the differentiation of colonic epithelium

De novo expression of human polypeptide N-acetylgalactosaminyltransferase 6 (GalNAc-T6) in colon adenocarcinoma inhibits the differentiation of colonic epithelium

LGR5 Promotes Breast Cancer Progression and Maintains Stem-Like Cells Through Activation of Wnt/β-Catenin Signaling

CD44-Positive Cancer Stem Cells Expressing Cellular Prion Protein Contribute to Metastatic Capacity in Colorectal Cancer

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