Transcriptional activation of the β‐<i>catenin</i> gene at the invasion front of colorectal liver metastases

Bandapalli, Obul Reddy; Dihlmann, Susanne; Helwa, Reham; Macher-Goeppinger, Stephan; Weitz, Jürgen; Schirmacher, Peter; Brand, Karsten

doi:10.1002/path.2539

Cited by 57 publications

(50 citation statements)

References 44 publications

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“…S5). As expected, the β-catenin (+) ECs expressed high levels of β-catenin/Tcf target genes, such as axin2, ccnd2a, ccnd2b, ctnnb1 and tcf7 (Bandapalli et al, 2009;Kioussi et al, 2002;Lustig et al, 2002;Roose et al, 1999) (Table 1). In addition, some of the Bmp signal-responsive genes, such as id1, id2a, id2b, smad6a and smad6b, were highly expressed in the β-catenin (+) ECs (Hollnagel et al, 1999;Ishida et al, 2000) ( Table 1), suggesting that β-catenin activity is stimulated by Bmp during CV development.…”

Section: Involvement Of Aggf1 In Bmp-induced CV Formationmentioning

confidence: 85%

β-catenin-dependent transcription is central to Bmp-mediated formation of venous vessels

et al. 2015

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β-catenin regulates the transcription of genes involved in diverse biological processes, including embryogenesis, tissue homeostasis and regeneration. Endothelial cell (EC)-specific gene-targeting analyses in mice have revealed that β-catenin is required for vascular development. However, the precise function of β-cateninmediated gene regulation in vascular development is not well understood, since β-catenin regulates not only gene expression but also the formation of cell-cell junctions. To address this question, we have developed a novel transgenic zebrafish line that allows the visualization of β-catenin transcriptional activity specifically in ECs and discovered that β-catenin-dependent transcription is central to the bone morphogenetic protein (Bmp)-mediated formation of venous vessels. During caudal vein (CV) formation, Bmp induces the expression of aggf1, a putative causative gene for KlippelTrenaunay syndrome, which is characterized by venous malformation and hypertrophy of bones and soft tissues. Subsequently, Aggf1 potentiates β-catenin transcriptional activity by acting as a transcriptional co-factor, suggesting that Bmp evokes β-catenin-mediated gene expression through Aggf1 expression. Bmp-mediated activation of β-catenin induces the expression of Nr2f2 (also known as Coup-TFII), a member of the nuclear receptor superfamily, to promote the differentiation of venous ECs, thereby contributing to CV formation. Furthermore, β-catenin stimulated by Bmp promotes the survival of venous ECs, but not that of arterial ECs. Collectively, these results indicate that Bmp-induced activation of β-catenin through Aggf1 regulates CV development by promoting the Nr2f2-dependent differentiation of venous ECs and their survival. This study demonstrates, for the first time, a crucial role of β-catenin-mediated gene expression in the development of venous vessels.

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Section: Involvement Of Aggf1 In Bmp-induced CV Formationmentioning

confidence: 85%

β-catenin-dependent transcription is central to Bmp-mediated formation of venous vessels

et al. 2015

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“…Βeta-catenin seems to belong to a different signalling pathway (wnt/β-catenin) and its significance in CRC remains equivocal. Βeta-catenin is a pivotal molecule involved in intercellular adhesion and some other oncogenic and developmental processes (49). The same study links the up-regulation of β-catenin with the confrontation of tumour cells in the host microenvironment, whilst in metastatic process.…”

Section: Discussionmentioning

confidence: 99%

KRAS Mutant Status, p16 and β-catenin Expression May Predict Local Recurrence in Patients Who Underwent Transanal Endoscopic Microsurgery (TEMS) for Stage I Rectal Cancer

Sideris

Moorhead

Díaz‐Cano

et al. 2016

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Abstract. Background The method of local excision, that has recently, gained wider acceptance, in early rectal cancer, is transanal endoscopic microsurgery (TEMS). TEMS generally offers advantages in operative access and oncological clearance over transanal resection (TAR), but recently a number of similar logic techniques with various rectal ports for endoscopic excision of rectal tumours has been invented. Those methods are collectively named transanal minimal-invasive surgery (TAMIS) and for oncological purposes they share the same features of local excision as TEMS (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).TEMS is a minimally invasive technique that was introduced by Buess in the early 1980's (2). Through the new rectoscope with 3D binocular optic and the endoscopic instruments, it offers better access to proximal lesions with lower margin positivity and fragmentation and magnification of the operative field (2, 15). TEMS is a safe procedure that offers low complication rates and peri-operative morbidity (10.7%) (4). There have been multiple studies to suggest that TEMS is the operation of choice for rectal adenomas (1), retrorectal and submucosal rectal lesions (5). Furthermore, TEMS offers the advantage of not damaging the anorectal function (7).TEMS is indicated as a curative treatment for malignant neoplasms that are histologically confirmed as pT1 sm1 carcinomas, whereas T1 sm2-3 and T2 lesions are still under question (8). A number of studies have shown that TEMS can have comparable results with radical surgery (1,8,12,16) for rectal cancer.There has been concern about oncologic outcomes following TEMS (17). Some studies support that there is potentially a higher risk of local recurrence rate with TEMS (8,10,18). Efforts have been made to classify risk with morphological and histological criteria with better patients' selection (1, 6-9); however, the risk stratification remains 5315

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“…Nuclear ␤-catenin increased with tumor progression, which was reported also for carcinoma of other origin, and to be independent of mutational activation. 36,37 Concomitantly, Shh expression was increased suggesting that also in hLSCC Wnt/␤-catenin acts upstream of Shh and becomes increasingly up-regulated with tumor malignancy. We speculated initially that the inhibitory function of Shh signaling might be impaired in hLSCC, leading to ␤-catenindriven tumor progression and invasion.…”

Section: Discussionmentioning

confidence: 99%

Sonic Hedgehog Acts as a Negative Regulator of β-Catenin Signaling in the Adult Tongue Epithelium

Schneider

Schänzer

Czupalla

et al. 2010

The American Journal of Pathology

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Wnt/␤-catenin signaling has been implicated in taste papilla development; however , its role in epithelial maintenance and tumor progression in the adult tongue remains elusive. We show Wnt/␤-catenin pathway activation in reporter mice and by nuclear ␤-catenin staining in the epithelium and taste papilla of adult mouse and human tongues. ␤-Catenin activation in APC min/؉ mice , which carry a mutation in adenomatous poliposis coli (APC), up-regulates Sonic hedgehog (Shh) and Jagged-2 (JAG2) in the tongue epithelium without formation of squamous cell carcinoma (SCC). We demonstrate that Shh suppresses ␤-catenin transcriptional activity in a signaling-dependent manner in vitro and in vivo. A similar regulation and function was observed for JAG2, suggesting that both pathways negatively regulate ␤-catenin, thereby preventing SCC formation in the tongue. This was supported by reduced nuclear ␤-catenin in the tongue epithelium of Patched ؉/؊ mice , exhibiting dominant active Shh signaling. At the invasive front of human tongue cancer , nuclear ␤-catenin and Shh were increased , suggesting their participation in tumor progression. Interestingly , Shh but not JAG2 was able to reduce ␤-catenin signaling in SCC cells , arguing for a partial loss of negative feedback on ␤-catenin transcription in tongue cancer. We show for the first time that the putative Wnt/␤-catenin targets Shh and JAG2 control ␤-catenin signaling in the adult tongue epithelium, a function that is partially lost in lingual SCC. (Am J

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Transcriptional activation of the β‐catenin gene at the invasion front of colorectal liver metastases

Cited by 57 publications

References 44 publications

β-catenin-dependent transcription is central to Bmp-mediated formation of venous vessels

β-catenin-dependent transcription is central to Bmp-mediated formation of venous vessels

KRAS Mutant Status, p16 and β-catenin Expression May Predict Local Recurrence in Patients Who Underwent Transanal Endoscopic Microsurgery (TEMS) for Stage I Rectal Cancer

Sonic Hedgehog Acts as a Negative Regulator of β-Catenin Signaling in the Adult Tongue Epithelium

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