NF-κB Signaling Pathway, Inflammation and Colorectal Cancer

Wang, So-Ly; Liu, Zhanjie; Lunshan, Wang; Zhang, Xiaoren

doi:10.1038/cmi.2009.43

Cited by 364 publications

(306 citation statements)

References 94 publications

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“…27,28 Numerous proangiogenic and proinflammatory genes, such as VEGF, IL-8 and COX-2, are transcriptionally regulated by the NF-kB pathway. 16 We found that GW9508 treatment elicited phosphorylated-IkBa at Ser32 in CRC cells, which is essential for the release of active NF-kB. However, blocking the activation of IkBa completely abrogated GPR120 signaling-induced production of VEGF, IL-8 and COX-2, and angiogenesis.…”

Section: Gpr120 Is Induced In Human Crc Tissues and Its Expression Ismentioning

confidence: 71%

“…GRP120 signaling induces angiogenesis in CRC cells through activation of the PI3K/Akt-NF-kB pathway GPR120 triggers various cellular pathways to exert disparate functions. 7,8 As the above-identified induced proangiogenic genes are known downstream targets of NF-kB, 16 we focused on the role of the NF-kB pathway in the production of proangiogenic mediators. First, we performed western blotting analysis to determine whether the NF-kB pathway was modulated by GPR120 signaling.…”

Section: Gpr120 Is Induced In Human Crc Tissues and Its Expression Ismentioning

confidence: 99%

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Identification of G-protein-coupled receptor 120 as a tumor-promoting receptor that induces angiogenesis and migration in human colorectal carcinoma

et al. 2013

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G-protein-coupled receptor 120 (GPR120) functions as a receptor for unsaturated long-chain free fatty acids and has an important role in regulating lipid and glucose metabolism. However, a role for GPR120 in the development of tumors has not yet been clarified. Here, we show that GPR120 signaling promotes angiogenic switching and motility of human colorectal carcinoma (CRC) cells. We show that the expression of GPR120 is significantly induced in CRC tissues and cell lines, which is associated with tumor progression. Activation of GPR120 signaling in human CRC promotes angiogenesis in vitro and in vivo, largely by inducing the expression and secretion of proangiogenic mediators such as vascular endothelial growth factor (VEGF), interleukin-8 and cyclooxygenase-2-derived prostaglandin E 2 . The PI3K/Akt-NF-kB pathway is activated by GPR120 signaling and is required for GPR120 signaling-induced angiogenic switching in CRC cells. And, GPR120 activation enhances the motility of CRC cells and induces epithelial-mesenchymal transition. Furthermore, in vivo study shows that activation of GPR120 promotes angiogenesis and tumor growth. Finally, we find that GPR120 expression is positively correlated with VEGF expression and inversely correlated with the epithelial marker E-cadherin in CRC tissues. Collectively, our results demonstrate that GPR120 functions as a tumor-promoting receptor in CRC and, therefore, shows promise as a new potential target for cancer therapeutics.

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Section: Gpr120 Is Induced In Human Crc Tissues and Its Expression Ismentioning

confidence: 71%

Section: Gpr120 Is Induced In Human Crc Tissues and Its Expression Ismentioning

confidence: 99%

Identification of G-protein-coupled receptor 120 as a tumor-promoting receptor that induces angiogenesis and migration in human colorectal carcinoma

et al. 2013

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“…Smad 2, 3 and 4) can be stimulated through Activin A binding with its ActRII receptor, linking both cell cytoskeleton remodeling and cell migration to quorum sensing peptide presence [28,43]. The upregulation of HIST1H4 can be associated with increased Notch1 stimulation, again connected to cancer metastasis, together with angiogenesis and NF-B production [30,44]; NF-B in turn contributes to the progression of colorectal cancer by regulating cell proliferation, angiogenesis and tumor metastasis [45]. Micro-RNA's block mRNA translation and thus impede the synthesis of specific proteins by recruiting the micro-RNA-induced silencing complex (miRISC) to target mRNAs [46]; downregulation of micro-RNA 222 and 644a thus increases KIT and -actin protein expression, respectively, thereby promoting endothelial cell proliferation and migration (angiogenesis) [36,47] and tumor cell invasiveness and motility [34].…”

Section: Discussionmentioning

confidence: 99%

Crosstalk between the microbiome and cancer cells by quorum sensing peptides

et al. 2015

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Highlights• Some quorum sensing peptides promote colon cancer cell invasion and angiogenesis.• Quorum sensing peptide Phr0662 influences tumor progression by EGFR targeting.• Cytokine profiles confirm the peptide's stimulatory effect on metastasis in vitro.• The microbiome-mammals crosstalk may explain the microbiome's effect on health. ABSTRACTTo date, the precise role of the human microbiome in health and disease states remains largely

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“…There is a wellestablished association between tumorigenesis and inflammation as suggested in numerous studies. [29][30][31] Given this, it would be of great interest to ascertain if the association with inflammation demonstrated here with EMAST does also lead to tumorigenesis, either primarily through downregulation of specific mismatch repair genes as shown previously in our lab 9 or secondarily via frameshift mutations of specific genes containing such tetranucleotide repeats in their sequences. It is our hope that this preliminary study demonstrating the high prevalence of EMAST would foster increased research that might help clarify the biological significance of EMAST.…”

Section: Discussionmentioning

confidence: 99%

973 Relationship of EMAST and Microsatellite Instability Among Patients With Rectal Cancer

Devaraj¹,

Ramamoorthy²,

Sandler³

et al. 2010

Gastroenterology

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Background Elevated microsatellite instability at selected tetranucleotide repeats (EMAST) is a genetic signature identified in 60% of sporadic colon cancers and may be linked with heterogeneous expression of the DNA mismatch repair (MMR) protein hMSH3. Unlike microsatellite instability-high (MSI-H) in which hypermethylation of hMLH1 occurs followed by multiple susceptible gene mutations, EMAST may be associated with inflammation and subsequent relaxation of MMR function with the biological consequences not known. We evaluated the prevalence of EMAST and MSI in a populationbased cohort of rectal cancers, as EMAST has not been previously determined in rectal cancers. Methods We analyzed 147 sporadic cases of rectal cancer using five tetranucleotide microsatellite markers and NationalCancer-Institute-recommended MSI (mononucleotide and dinucleotide) markers. EMAST and MSI determinations were made on analysis of DNA sequences of the polymerase chain reaction products and determined positive if at least two loci were found to have frame-shifted repeats upon comparison between normal and cancer samples from the same patient. We correlated EMAST data with race, gender, and tumor stage and examined the samples for lymphocyte infiltration. Results Among this cohort of patients with rectal cancer (mean age 62.2±10.3 years, 36% female, 24% African American), 3/147 (2%) showed MSI (three males, two African American) and 49/147 (33%) demonstrated EMAST. Rectal tumors from African Americans were more likely to show EMAST than Caucasians (18/37, 49% vs. 27/104, 26%, p=0.014) and were associated with advanced stage (18/29, 62% EMAST vs. 18/53, 37%, non-EMAST p=0.02). There was no association between EMAST and gender. EMAST was more prevalent in rectal tumors that showed peri-tumoral infiltration compared to those without (30/49, 60% EMAST vs. 24/98, 25% non-EMAST, p=0.0001). Conclusions EMAST in rectal cancer is common and MSI is rare. EMAST is associated with African-American race and may be more commonly seen with metastatic disease. The etiology and consequences of EMAST are under investigation, but its association with immune cell infiltration suggests that inflammation may play a role for its development.

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NF-κB Signaling Pathway, Inflammation and Colorectal Cancer

Cited by 364 publications

References 94 publications

Identification of G-protein-coupled receptor 120 as a tumor-promoting receptor that induces angiogenesis and migration in human colorectal carcinoma

Identification of G-protein-coupled receptor 120 as a tumor-promoting receptor that induces angiogenesis and migration in human colorectal carcinoma

Crosstalk between the microbiome and cancer cells by quorum sensing peptides

973 Relationship of EMAST and Microsatellite Instability Among Patients With Rectal Cancer

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