Tumour–stroma interactions in colorectal cancer: converging on β-catenin activation and cancer stemness

Le, Ngoc Hang; Franken, Patrick; Fodde, Riccardo

doi:10.1038/sj.bjc.6604401

Cited by 94 publications

(83 citation statements)

References 64 publications

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“…The PI3K pathway is involved in the function of leukocytes and endothelial cells and they appear to be crucial mediators of inflammatory reactions (Le and Fodde, 2008). As a vital signalling pathway in the innate immune response, PI3K is involved in chemotaxis of neutrophils and macrophages to the site of inflammation (Morrison et al, 2012) and this may be another mechanism by which it is involved in carcinogenesis.…”

Section: Pi3kmentioning

confidence: 99%

“…The direct tumoral effects of the PI3K pathway include inhibition of apoptosis, increased cellular proliferation and growth and a reduction in cell-cycle arrest (Le and Fodde, 2008). The PI3K pathway is involved in the function of leukocytes and endothelial cells and they appear to be crucial mediators of inflammatory reactions (Le and Fodde, 2008).…”

Section: Pi3kmentioning

confidence: 99%

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The role of dietary polyphenols in the moderation of the inflammatory response in early stage colorectal cancer

Little

Combet

McMillan

et al. 2015

Critical Reviews in Food Science and Nutrition

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Current focus in colorectal cancer management is on reducing overall colorectal cancer mortality by increasing the number of early stage cancers diagnosed and treated with curative intent. There is good evidence that screening for colorectal cancer increases the number of early-stage cancers diagnosed and leads to a reduction of cancer specific mortality. Despite the success of the colorectal cancer screening programme in down-staging colorectal cancer, interval cancer rates are substantial and other strategies to reduce colorectal cancer risk and disease recurrence after surgery with curative intent are desirable.

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Section: Pi3kmentioning

confidence: 99%

Section: Pi3kmentioning

confidence: 99%

The role of dietary polyphenols in the moderation of the inflammatory response in early stage colorectal cancer

Little

Combet

McMillan

et al. 2015

Critical Reviews in Food Science and Nutrition

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show abstract

“…When Wnt signalling is activated, normal cell differentiation and proliferation are modified, leading to probable cancer genesis (129) . Furthermore, the relative levels of Wnt signalling determine whether cells proliferate or go to apoptosis (126) , since several in vivo studies support the evidence that increased activation of Wnt transcriptional activity enhances apoptosis in some cancerous cells.…”

Section: Apoptosismentioning

confidence: 99%

“…In the large intestine, cell proliferation, differentiation and positional localisation along the crypt axis are governed by several signalling pathways including the Wnt/b-catenin pathway (129) . When Wnt signalling is activated, normal cell differentiation and proliferation are modified, leading to probable cancer genesis (129) .…”

Section: Apoptosismentioning

confidence: 99%

From the gut to the peripheral tissues: the multiple effects of butyrate

et al. 2010

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Butyrate is a natural substance present in biological liquids and tissues. The present paper aims to give an update on the biological role of butyrate in mammals, when it is naturally produced by the gastrointestinal microbiota or orally ingested as a feed additive. Recent data concerning butyrate production delivery as well as absorption by the colonocytes are reported. Butyrate cannot be detected in the peripheral blood, which indicates fast metabolism in the gut wall and/or in the liver. In physiological conditions, the increase in performance in animals could be explained by the increased nutrient digestibility, the stimulation of the digestive enzyme secretions, a modification of intestinal luminal microbiota and an improvement of the epithelial integrity and defence systems. In the digestive tract, butyrate can act directly (upper gastrointestinal tract or hindgut) or indirectly (small intestine) on tissue development and repair. Direct trophic effects have been demonstrated mainly by cell proliferation studies, indicating a faster renewal of necrotic areas. Indirect actions of butyrate are believed to involve the hormono-neuro-immuno system. Butyrate has also been implicated in down-regulation of bacteria virulence, both by direct effects on virulence gene expression and by acting on cell proliferation of the host cells. In animal production, butyrate is a helpful feed additive, especially when ingested soon after birth, as it enhances performance and controls gut health disorders caused by bacterial pathogens. Such effects could be considered for new applications in human nutrition

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“…It is becoming clear that tumors are heterogenous with regard to molecular and immunophenotypical features and therefore an 'overall' estimate of protein expression may obscure changes in specific areas, such as the advancing tumor margin in which processes, such as epithelial-mesenchymal transition, are most active. 11,17 We have noted earlier that endometrial carcinomas exhibiting a distinctive pattern of invasion comprising microcystic, elongated and fragmented ('MELF') glands 18 show specific pathological associations and morphological changes, some of which are suggestive of epithelial-mesenchymal transition. 19,20 Therefore, in this study, we have further explored the cellular alterations at the invasive margin of endometrial adenocarcinoma by comparing the expression of the cell-cycle-related proteins, cyclin D1, b-catenin and p16, between conventional tumor areas and foci exhibiting MELF pattern invasion.…”

mentioning

confidence: 99%

Expression of cell cycle regulatory proteins in endometrial adenocarcinoma: variations in conventional tumor areas and in microcystic, elongated and fragmented glands

et al. 2009

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Endometrial adenocarcinomas may show a distinctive pattern of invasion characterized by the presence of microcystic, elongated and fragmented glands, often most evident along the advancing tumor margin. Earlier, we have shown that these changes appear restricted to low-grade endometrioid carcinomas, many of which show focal mucinous differentiation and lymphovascular space invasion. However, the molecular alterations associated with this morphological alteration are not known. In this study, we have examined immunoreactivity for the cell cycle regulatory proteins cyclin D1, p16 and b-catenin in 22 endometrial carcinomas, specifically comparing the results in conventional tumor areas and in foci in which the glands exhibited microcystic, elongated and fragmented appearances. The conventional neoplastic glands exhibited cyclin D1 and p16 expression in most cases, with 450% tumor cells positive in 8 cases and 11 tumors, respectively. Membranous expression of b-catenin was usually preserved, with variable cytoplasmic and nuclear staining. Cyclin D1 and b-catenin predominantly stained cells at the peripheral or basal aspect of the conventional glands, whereas p16 was more uniformly expressed centrally. Tumor foci composed of microcystic, fragmented and elongated glands showed strong expression of cyclin D1 and p16, sometimes in contrast to unstained contiguous or adjacent conventional neoplastic elements, and there was also loss or fragmentation of membranous b-catenin staining. Intravascular tumor cells also expressed cyclin D1 and p16 and therefore the immunostains often highlighted subtle foci of lymphovascular invasion. The heterogenous expression of cell cycle regulatory proteins within endometrial adenocarcinoma illustrates the importance of assessing microanatomical variations in immunoreactivity, particularly at the advancing margin of tumors. The upregulation of cyclin D1 and p16, together with loss of membranous b-catenin expression in microcystic, fragmented and elongated glands, is similar to epithelial-mesenchymal transitions observed in other malignancies and suggests that this pattern of invasion represents an active rather than a degenerative cellular process. Modern Pathology (2009) 22, 725-733; doi:10.1038/modpathol.2009 published online 6 March 2009 Keywords: endometrial; carcinoma; invasion; MELF; epithelial-mesenchymal transition; immunohistochemistry Endometrial carcinomas can be divided into two major groups on the basis of clinicopathological, immunohistological and molecular features. 1,2 The more common (type 1) subgroup accounts for 80-85% of cases and mainly comprises endometrioid adenocarcinomas of low-to-intermediate grade. These tumors typically occur in perimenopausal and younger postmenopausal patients, often arise in hyperestrogenic states and are associated with atypical endometrial hyperplasia/endometrial intraepithelial neoplasia. Frequently, type 1 carcinomas are confined to the uterine corpus at the time of diagnosis (stage 1), and the prognosis in such patients is generally ...

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Tumour–stroma interactions in colorectal cancer: converging on β-catenin activation and cancer stemness

Cited by 94 publications

References 64 publications

The role of dietary polyphenols in the moderation of the inflammatory response in early stage colorectal cancer

The role of dietary polyphenols in the moderation of the inflammatory response in early stage colorectal cancer

From the gut to the peripheral tissues: the multiple effects of butyrate

Expression of cell cycle regulatory proteins in endometrial adenocarcinoma: variations in conventional tumor areas and in microcystic, elongated and fragmented glands

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