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How a high-fat diet boosts colorectal cancer stem cells.

CLEVELAND, Ohio, July 6, 2017 -- Poor diet is associated with 80 percent of colorectal cancer cases, but the exact pathways by which diet leads to cancer have not been known.

But in a newly published study, Cleveland Clinic researchers identified a specific molecular pathway that plays a key role in the link between a high-fat diet and tumor growth in the colon.

Colorectal cancer is the third most common cancer in the United States with more than 130,000 cases reported annually.

Scientists have known for a while that the disease arises from several genetic, epigenetic and environmental causes, including diet.

The researchers showed in preclinical models that cancer stem cell growth in the colon was enhanced by a high-fat Western diet.

Cancer stem cells are a subset of resilient, aggressive malignant cells that are believed to be partially responsible for spread and recurrence of cancer.

When the researchers blocked the JAK2-STAT3 cellular signaling pathway, a widely studied pathway known to promote tumor growth, the spike in cancer stem cell growth caused by the high-fat diet declined.

This study provides more insight into how the JAK2-STAT3 pathway is linked to diet-related cancer.

Pinpointing the exact mechanism can help researchers develop therapeutics to counteract the negative effects of a Western diet on colorectal cancer.

"These new findings are the first to show the connection between high-fat intake and colon cancer via a specific molecular pathway," said Matthew Kalady of the Cleveland Clinic. "We can now build upon this knowledge to develop new treatments aimed at blocking this pathway and reducing the negative impact of a high-fat diet on colon cancer risk."

The team analyzed human colorectal cancer-free survival data in the Cancer Genome Atlas.

They then gaged primary and metastasized colorectal cancer specimens using microarray analysis.

They further verified the link between high-fat diet and stem cell maintenance in obesity-resistant mice.

The findings could provide a way to regulate cancer stem cells. And they could show how environmental factors like diet can change cancer stem cell populations in advanced cancers.

Citation: Sheelarani Karunanithi et al., "RBP4-STRA6 Pathway Drives Cancer Stem Cell Maintenance and Mediates High-Fat Diet-Induced Colon Carcinogenesis," Stem Cell Reports, July 2017 DOI: 10.1016/j.stemcr.2017.06.002


Contact: Matthew F. Kalady,

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Title Annotation:Stem Cells & Cancer
Publication:Stem Cell Research News
Date:Jul 17, 2017
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