Modeling Colitis-Associated Cancer with Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS)

Thaker, Ameet I.; Shaker, Anisa; Rao, Mahil; Ciorba, Matthew A.

doi:10.3791/4100

Cited by 128 publications

(128 citation statements)

References 21 publications

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“…2H). As reported (25), histologically a majority of carcinomas were observed and no metastatic lesion was evident after 10 weeks of AOM/DSS treatment (Supplementary Fig. 2B).…”

Section: Resultssupporting

confidence: 84%

STRAP Promotes Stemness of Human Colorectal Cancer via Epigenetic Regulation of the NOTCH Pathway

Lin

Yuan

et al. 2017

Cancer Research

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NOTCH signaling exerts essential roles in normal and malignant intestinal physiology and the homeostasis of cancer stem-like cells (CSC), but the basis for this latter role remains obscure. The signaling scaffold protein STRAP is upregulated in several cancers where it promotes tumorigenicity and metastasis. Here we report a novel oncogenic function for STRAP in maintaining CSC subpopulations in a heterogeneous mixture by antagonizing formation of the chromatin modifier PRC2 and by epigenetically activating NOTCH signals in human colorectal cancer (CRC). Silencing STRAP sensitized CRC cells to chemotherapeutic drugs in vitro and in vivo. STRAP depletion also contributed to a reduced stem-like phenotype of CRC cells, as indicated by reduced expression of the CSC signature and NOTCH signaling regulators in vitro and by diminished tumorigenesis in vivo. Genes encoding some upstream activators of NOTCH were highly enriched for H3K27me3, which form repressive chromatin domains upon STRAP silencing. Mechanistically, STRAP competitively disrupted association of the PRC2 subunits EZH2 and SUZ12, thereby inhibiting PRC2 assembly. Restoring the NOTCH pathway by lentiviral expression of NICD1 or HES1 in STRAP-depleted tumor cells reversed the CSC phenotype. In 90 CRC clinical specimens, a significant positive correlation was documented between the expression of STRAP and HES1. Overall, our findings illuminated a novel STRAP-NOTCH1-HES1 molecular axis as a CSC regulator in CRC, with potential implications to improve treatment of this disease.

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“…2H). As reported (25), histologically a majority of carcinomas were observed and no metastatic lesion was evident after 10 weeks of AOM/DSS treatment (Supplementary Fig. 2B).…”

Section: Resultssupporting

confidence: 84%

STRAP Promotes Stemness of Human Colorectal Cancer via Epigenetic Regulation of the NOTCH Pathway

Lin

Yuan

et al. 2017

Cancer Research

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“…In this study, AOM treatment was used to increase the basal level of colorectal tumorigenesis but not for direct induction of colorectal tumor formation, so that oncogenic effects of E. coli could be detected. On day 0, mice were intraperitoneally injected with AOM (10 mg/kg), according to a published protocol (13). On day 5, mice were treated with neomycin (1 g/L), vancomycin (0.5 g/L), ampicillin (1 g/L), and metronidazole (1 g/L) in drinking water to eliminate commensal flora (14) and facilitate the colonization of fed bacteria.…”

Section: Mouse Models For Colorectal Tumorigenesismentioning

confidence: 99%

“…On day 5, mice were treated with neomycin (1 g/L), vancomycin (0.5 g/L), ampicillin (1 g/L), and metronidazole (1 g/L) in drinking water to eliminate commensal flora (14) and facilitate the colonization of fed bacteria. Dextran sulfate sodium (DSS) is typically used together with AOM to induce colorectal cancer in mice (13). However, the oncogenic action of the combination of AOM and DSS are strong and may overshadow the oncogenic effects of fed bacteria.…”

Section: Mouse Models For Colorectal Tumorigenesismentioning

confidence: 99%

Hemolytic E. coli Promotes Colonic Tumorigenesis in Females

Tang

et al. 2016

Cancer Research

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“…The risk to IBD patients of developing cancer is proportional to the duration and extent of inflammation, hence the development of CAC (43). In particular, colonic dysplasia in IBD and colon cancer is thought to be the result of repeated cycles of epithelial cell injury and repair (44). In this study we used the combined AOM/DSS murine model that reproduces core features of human CAC (33).…”

Section: Malmentioning

confidence: 99%

MyD88 adaptor-like (Mal) regulates intestinal homeostasis and colitis-associated colorectal cancer in mice

Aviello

Corr

Johnston

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Modeling Colitis-Associated Cancer with Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS)

Cited by 128 publications

References 21 publications

STRAP Promotes Stemness of Human Colorectal Cancer via Epigenetic Regulation of the NOTCH Pathway

STRAP Promotes Stemness of Human Colorectal Cancer via Epigenetic Regulation of the NOTCH Pathway

Hemolytic E. coli Promotes Colonic Tumorigenesis in Females

MyD88 adaptor-like (Mal) regulates intestinal homeostasis and colitis-associated colorectal cancer in mice

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