MAP kinase genes and colon and rectal cancer

Slattery, Martha L.; Lundgreen, Abbie; Wolff, Roger K.

doi:10.1093/carcin/bgs305

Cited by 100 publications

(79 citation statements)

References 24 publications

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“…MAP2K1 has been identified as an occasional driver in non-small cell lung cancer [57], and sustained gain-of-function mutations in melanoma [58]. Variation among genes in the MAPK pathway predisposes to colon and rectal cancer, including susceptibility variants in MAP2K1 [59]. …”

Section: Resultsmentioning

confidence: 99%

Epigenomic annotation of noncoding mutations identifies mutated pathways in primary liver cancer

Lowdon

Wang

2017

PLoS ONE

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Evidence that noncoding mutation can result in cancer driver events is mounting. However, it is more difficult to assign molecular biological consequences to noncoding mutations than to coding mutations, and a typical cancer genome contains many more noncoding mutations than protein-coding mutations. Accordingly, parsing functional noncoding mutation signal from noise remains an important challenge. Here we use an empirical approach to identify putatively functional noncoding somatic single nucleotide variants (SNVs) from liver cancer genomes. Annotation of candidate variants by publicly available epigenome datasets finds that 40.5% of SNVs fall in regulatory elements. When assigned to specific regulatory elements, we find that the distribution of regulatory element mutation mirrors that of nonsynonymous coding mutation, where few regulatory elements are recurrently mutated in a patient population but many are singly mutated. We find potential gain-of-binding site events among candidate SNVs, suggesting a mechanism of action for these variants. When aggregating noncoding somatic mutation in promoters, we find that genes in the ERBB signaling and MAPK signaling pathways are significantly enriched for promoter mutations. Altogether, our results suggest that functional somatic SNVs in cancer are sporadic, but occasionally occur in regulatory elements and may affect phenotype by creating binding sites for transcriptional regulators. Accordingly, we propose that noncoding mutation should be formally accounted for when determining gene- and pathway-mutation burden in cancer.

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Section: Resultsmentioning

confidence: 99%

Epigenomic annotation of noncoding mutations identifies mutated pathways in primary liver cancer

Lowdon

Wang

2017

PLoS ONE

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“…Mitogen-activated protein kinases (MAPKs), a family of serine-threonine protein kinases, are important in controlling cell proliferation, differentiation, migration and apoptosis (Ragusa et al, 2012;Slattery et al, 2012;Yang et al, 2013b;Lin et al, 2015). In this study, we measured the phosphorylation of the major MAPK proteins, including Akt, p38, ERK1/2, and JNK using Western blotting, and the results showed that RIE suppressed the phosphorylation of ERK1/2 protein.…”

Section: Discussionmentioning

confidence: 98%

Rubus idaeusInhibits Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Suppression of MMP-2 through Modulation of the ERK1/2 Pathway

et al. 2017

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Nasopharyngeal carcinoma (NPC) is characterized by a high incidence of metastasis in the neck lymph nodes, resulting in a poor prognosis and posing challenges for treatment. In this study, we investigated the in vitro antimetastatic properties of Rubus idaeus extract (RIE) on human nasopharyngeal carcinoma cells. HONE-1, NPC-39 and NPC-BM cells were subjected to RIE treatment, and effects on the migration and invasion of tumor cells were analyzed. The results showed that RIE suppressed the migration and invasion of NPC cells. Gelatin zymography assay, Western blotting and real-time PCR showed that matrix metalloproteinases-2 (MMP-2) enzyme activity, protein expression and mRNA levels were down-regulated by RIE treatment. To identify the signaling pathway, mitogen-activated protein kinase proteins were examined, which showed that phosphorylation of ERK1/2 was inhibited after the treatment of RIE. In summary, our data showed that RIE inhibited the migration and invasion of NPC cells by suppressing the expression of MMP-2 by The American Journal of Chinese Medicine, Vol. 45, No. 7, 1557-1572© 2017 down-regulating the ERK1/2 signaling pathway, suggesting that Rubus idaeus may serve as chemotherapeutic and chemopreventive agent for NPC.

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“…It is known that the MAP kinase and Akt pathways play important roles in colon cancer cell invasion and migration (Tremblay et al 2006, Huynh et al 2010, Slattery et al 2012. The activation of Akt signaling promotes EMT and tumor growth in colon cancer cells (Suman et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Brain-derived neurotrophic factor regulates cell motility in human colon cancer

Huang¹,

Lin²,

Lin³

et al. 2015

Endocrine-Related Cancer

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Brain-derived neurotrophic factor (BDNF) is a potent neurotrophic factor that has been shown to affect cancer cell metastasis and migration. In the present study, we investigated the mechanisms of BDNF-induced cell migration in colon cancer cells. The migratory activities of two colon cancer cell lines, HCT116 and SW480, were found to be increased in the presence of human BDNF. Heme oxygenase-1 (HO)-1 is known to be involved in the development and progression of tumors. However, the molecular mechanisms that underlie HO-1 in the regulation of colon cancer cell migration remain unclear. Expression of HO-1 protein and mRNA increased in response to BDNF stimulation. The BDNF-induced increase in cell migration was antagonized by a HO-1 inhibitor and HO-1 siRNA. Furthermore, the expression of vascular endothelial growth factor (VEGF) also increased in response to BDNF stimulation, as did VEGF mRNA expression and transcriptional activity. The increase in BDNF-induced cancer cell migration was antagonized by a VEGF-neutralizing antibody. Moreover, transfection with HO-1 siRNA effectively reduced the increased VEGF expression induced by BDNF. The BDNF-induced cell migration was regulated by the ERK, p38, and Akt signaling pathways. Furthermore, BDNF-increased HO-1 and VEGF promoter transcriptional activity were inhibited by ERK, p38, and AKT pharmacological inhibitors and dominantnegative mutants in colon cancer cells. These results indicate that BDNF increases the migration of colon cancer cells by regulating VEGF/HO-1 activation through the ERK, p38, and PI3K/Akt signaling pathways. The results of this study may provide a relevant contribution to our understanding of the molecular mechanisms by which BDNF promotes colon cancer cell motility.

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MAP kinase genes and colon and rectal cancer

Cited by 100 publications

References 24 publications

Epigenomic annotation of noncoding mutations identifies mutated pathways in primary liver cancer

Epigenomic annotation of noncoding mutations identifies mutated pathways in primary liver cancer

Rubus idaeusInhibits Migration and Invasion of Human Nasopharyngeal Carcinoma Cells by Suppression of MMP-2 through Modulation of the ERK1/2 Pathway

Brain-derived neurotrophic factor regulates cell motility in human colon cancer

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