Helicobacter pylori is the strongest known risk factor for gastric carcinogenesis. One cancer-linked locus is the cag pathogenicity island, which translocates components of peptidoglycan (PGN) into host cells. NOD1 is an intracellular immune receptor that senses PGN from Gram-negative bacteria and responds by inducing autophagy and activating NF-κB, leading to inflammation-mediated bacterial clearance; however chronic pathogens can evade NOD1-mediated clearance by altering PGN structure. We previously demonstrated that the H. pylori cag+ strain 7.13 rapidly induces gastric cancer in Mongolian gerbils. Using 2D-DIGE and mass spectrometry, we identified a novel mutation within the gene encoding the peptidoglycan deacetylase PgdA; therefore, we sought to define the role of H. pylori PgdA in NOD1-dependent activation of NF-κB, inflammation, and cancer. Co-culture of H. pylori strain 7.13 or its pgdA- isogenic mutant with AGS gastric epithelial cells or HEK293 epithelial cells expressing a NF-κB reporter revealed that pgdA inactivation significantly decreased NOD1-dependent NF-κB activation and autophagy. Infection of Mongolian gerbils with an H. pylori pgdA- mutant strain led to significantly decreased levels of inflammation and malignant lesions in the stomach; however, pre-activation of NOD1 prior to bacterial challenge reciprocally suppressed inflammation and cancer in response to wild-type H. pylori. Expression of NOD1 differs in human gastric cancer specimens compared to non-cancer samples harvested from the same patients. These results indicate that PGN deacetylation plays an important role in modulating host inflammatory responses to H. pylori, allowing the bacteria to persist and induce carcinogenic consequences in the gastric niche.

The Colon Cancer Alliance (CCA) is a community that provides hope and support to patients and their families, while saving lives through screening, access, awareness, advocacy and research.

Why should you wear blue? That’s the question the Colon Cancer Alliance (CCA) wants communities, businesses and individuals across the country (and even the world) to answer during its Dress in Blue Day program on Friday, March 6th 2015.

The Alliance’s National Dress in Blue Day takes place every year on the first Friday in March, as the official kickoff to National Colorectal Cancer Month.

The program promotes awareness of colon cancer, encourages people to get their colon checked and ultimately, is working to put an end to this often preventable disease. On this special day, thousands of people throughout the United States will be showing their support by dressing in blue and talking to people about colon cancer and screening.

Show Us Your Blue

Look for photos on our @PennCancer Facebook page and share your own. Together we can help raise awareness for Colorectal Cancer.

Facts About Colorectal Cancer

Currently, colorectal cancer affects about 1 in 20 people – with some at greater risk due to age, race, and diabetes.

More than 143,000 Americans will be diagnosed with the disease this year and 51,690 people will lose their battle with the disease.

But there is good news: Colon cancer is often beatable when detected and treated in its early stages or can be prevented altogether when polyps are removed before they develop into cancer.

Dress in Blue Day works to make sure everyone knows this – encouraging local communities, businesses and the general public to support awareness of colon cancer by dressing in blue and hosting educational events.

This March, help us spread colon cancer awareness – it could save someone’s life!

Wear blue to support colon cancer awareness. 

The Colon Cancer Alliance (CCA) is a community that provides hope and support to patients and their families, while saving lives through screening, access, awareness, advocacy and research.

Why should you wear blue? That’s the question the Colon Cancer Alliance (CCA) wants communities, businesses and individuals across the country (and even the world) to answer during its Dress in Blue Day program on Friday, March 6th 2015.

The Alliance’s National Dress in Blue Day takes place every year on the first Friday in March, as the official kickoff to National Colorectal Cancer Month.

The program promotes awareness of colon cancer, encourages people to get their colon checked and ultimately, is working to put an end to this often preventable disease. On this special day, thousands of people throughout the United States will be showing their support by dressing in blue and talking to people about colon cancer and screening.

Show Us Your Blue

Look for photos on our @PennCancer Facebook page and share your own. Together we can help raise awareness for Colorectal Cancer.

Facts About Colorectal Cancer

Currently, colorectal cancer affects about 1 in 20 people – with some at greater risk due to age, race, and diabetes.

More than 143,000 Americans will be diagnosed with the disease this year and 51,690 people will lose their battle with the disease.

But there is good news: Colon cancer is often beatable when detected and treated in its early stages or can be prevented altogether when polyps are removed before they develop into cancer.

Dress in Blue Day works to make sure everyone knows this – encouraging local communities, businesses and the general public to support awareness of colon cancer by dressing in blue and hosting educational events.

This March, help us spread colon cancer awareness – it could save someone’s life!

Although many studies have uncovered an important role for the receptor-binding protein kinase RIP1 in controlling cell death signaling, its possible contributions to cancer pathogenesis have been little explored. Here, we report that RIP1 functions as an oncogenic driver in human melanoma. Although RIP1 was commonly upregulated in melanoma, RIP1 silencing inhibited melanoma cell proliferation in vitro and retarded the growth of melanoma xenografts in vivo. Conversely, while inducing apoptosis in a small proportion of melanoma cells, RIP1 overexpression enhanced proliferation in the remaining cells. Mechanistic investigations revealed that the proliferative effects of RIP1 overexpression were mediated by NF-κB activation. Strikingly, ectopic expression of RIP1 enhanced the proliferation of primary melanocytes, triggering their anchorage-independent cell growth in an NF-κB–dependent manner. We identified DNA copy-number gain and constitutive ubiquitination by a TNFα autocrine loop mechanism as two mechanisms of RIP1 upregulation in human melanomas. Collectively, our findings define RIP1 as an oncogenic driver in melanoma, with potential implications for targeting its NF-κB–dependent activation mechanism as a novel approach to treat this disease. Cancer Res; 75(8); 1–13. ©2015 AACR.