Ski/SnoN expression in the sequence metaplasia-dysplasia-adenocarcinoma of Barrett's esophagus

Villanacci, Vincenzo; Bellone, Graziella; Battaglia, Edda; Rossi, Elisa; Carbone, Anna; Prati, Adriana; Verna, C.; Niola, Paolo; Morelli, Antonio; Grassini, Mario; Bassotti, Gabrio

doi:10.1016/j.humpath.2007.07.009

Cited by 25 publications

(30 citation statements)

References 37 publications

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“…8 The C184M protein induces the cytoplasmic accumulation of c-Ski, and the C184M-Ski complex negatively regulates TGFβ signaling by inhibiting the nuclear translocation of the Smads . 9 The interaction of c-Ski with TβRI suppresses nuclear accumulation of the Smads complex; this occurs as a consequence of the sequestration of this complex by TβRI (Ferrand et al 2010) b carcinoma (Fukuchi et al 2004), Barrett's esophagus (Villanacci et al 2008), leukemia (Ritter et al 2006), colorectal cancer (Bravou et al 2009), gastric cancer (Takahata et al 2009), pancreatic cancer (Heider et al 2007;Wang et al 2009Wang et al ), hemangiomas (O et al 2009), and melanoma (Boone et al 2009;Reed et al 2001). Further evidence supporting the pro-oncogenic function of c-Ski in tumor progression comes from studies of various human cancer cell lines (Fig.…”

Section: C-ski In Cancer Progressionmentioning

confidence: 99%

“…Originally, c-Ski was identified as a nuclear protein Colmenares et al 1991a;Sutrave et al 1990a), and more recent work has identified a nuclear localization signal in human c-Ski (Nagata et al 2006). However, in tumor cells of virtually all analyzed specimens, c-Ski is reported to localize also to the cytoplasm, which might enhance its growth-promoting properties (Bravou et al 2009;Fukuchi et al 2004;Heider et al 2007;Reed et al 2001;Villanacci et al 2008). Mechanisms employed by cytoplasmic c-Ski, such as the promotion of cell proliferation by sequestering the tumor suppressor Rb to the cytoplasm (Jacob et al 2008) or the inhibition of TGFβ signaling by interfering with its cytoplasmic intermediates (Ferrand et al 2010;Kokura et al 2003;Prunier et al 2003), have been proposed (Fig.…”

Section: C-ski In Cancer Progressionmentioning

confidence: 99%

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c-Ski in health and disease

Bonnon

Atanasoski

2011

Cell Tissue Res

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c-Ski is an evolutionary conserved protein that is involved in diverse cellular processes such as proliferation, differentiation, transformation, and tumor progression. A large range of cellular partners of c-Ski, including transcription factors, chromatin-remodeling molecules, tumor suppressors, and nuclear hormone receptors, has been identified. Moreover, numerous mechanisms have been described by which c-Ski regulates essential signaling pathways, e.g., the TGFβ pathway. In this review, we summarize the diverse roles attributed to c-Ski during normal development and in cancer progression and discuss future strategies to unravel further the complex nature of c-Ski actions in a context-dependent manner.

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Section: C-ski In Cancer Progressionmentioning

confidence: 99%

Section: C-ski In Cancer Progressionmentioning

confidence: 99%

c-Ski in health and disease

Bonnon

Atanasoski

2011

Cell Tissue Res

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“…Among the negative regulators of this signaling, c-Ski plays an important role in carcinogenesis. Indeed, overexpression of c-Ski induces morphologic transformation in chicken and quail embryo fibroblasts, and elevated levels of c-Ski have been detected in human tumors (2)(3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

“…As c-Ski also associates with the corepressors N-CoR and Sin3A (12), it has been postulated that the mechanism through which c-Ski suppresses TGF-β signaling relies on repression of Smad transcriptional activity (13). However, several recent studies have shown that c-Ski also resides in the cytoplasm, suggesting that alternative mechanisms of repression of TGF-β signaling by c-Ski might also exist (6,7,(14)(15)(16)(17). Consistent with this, previous data from our laboratory and others have indicated that expression of c-Ski can induce a constitutive association of Smad4 with Smad2 or Smad3 (15,18).…”

Section: Introductionmentioning

confidence: 99%

The Oncoprotein c-Ski Functions as a Direct Antagonist of the Transforming Growth Factor-β Type I Receptor

2010

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The oncoprotein c-Ski has been implicated in the negative regulation of transforming growth factor-β (TGF-β) signaling owing to its ability to repress Smad transcriptional activity via recruitment of a transcriptional corepressor complex containing histone deacetylases. However, c-Ski has also been shown to localize to the cytoplasm, raising the interesting possibility that it might disable TGF-β signaling through alternative mechanisms. Here, we provide evidence that c-Ski can restrict TGF-β signaling by interacting directly with the activated TGF-β type I receptor (TβRI). We explored the physiologic relevance of the c-Ski/TβRI interaction and found that it can culminate in a constitutive association of TβRI with a nonfunctional R-Smad/Smad4 complex. Based on these findings, we hypothesize that the interaction between c-Ski and TβRI might interfere with nuclear translocation of the R-Smad/Smad4 complex, thereby attenuating TGF-β signaling. Such a mechanism may play a crucial role in tumor progression, because many tumors that express high levels of c-Ski also display impaired nuclear accumulation of Smads. Cancer Res; 70(21); 8457-66. ©2010 AACR.

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“…The genes involved in the development of Barrett's metaplasia seem to be: p16, APC, Rb, p53, DCC which are lost in this early step. Moreover, cyclin D1 could be amplified, p53 mutated, APC hypermethylated and Bcl2, iNOS, COX-2, CDX2, SRC, SKI, SnoN overexpressed (9)(10)(11).…”

Section: From Metaplasia To Adenocarcinomamentioning

confidence: 99%

Influence of genetics on tumoral pathologies: The example of the adenocarcinoma arising in Barrett's esophagus

Villanacci

Bassotti

Salemme

et al. 2012

Rev. esp. enferm. dig.

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Barrett's esophagus (BE) refers to an abnormal change (metaplasia) in the cells of the inferior portion of the esophagus. About 10% of patients with symptomatic gastroesophageal reflux disease (GERD) have BE. In some cases, BE develops as an advanced stage of erosive esophagitis. The risk of esophageal cancer appears to be increased in patients with BE. The only way to diagnose BE is by endoscopy and histology. Some studies suggest that intensive treatment of Barrett's esophagus with effective acid suppression can reduce the amount of abnormal lining in the esophagus. It is not clear whether such treatment also prevents esophageal cancer. Generally, the cancer starts out as carcinoma of the esophagus on the surface, and then invades the surrounding tissue. Surgery offers the best chance of long-term survival. There are many events that occur in Barrett's esophagus that lead to the development of cancer and most of them appear to occur early, before high-grade dysplasia or cancer develops. No one knows what the late events are and how cells acquire the ability to leave their normal growth boundaries. It is now widely accepted that the development of most cancers is due to something called genomic or genetic instability. The aim of this review is to show BE pathology in its progression to cancer looking for new biomarkers to distinguish between BE -dysplasia (low grade and high grade)-adenocarcinoma (ADC) and to characterize the ADC, giving more hope for its treatment.

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Ski/SnoN expression in the sequence metaplasia-dysplasia-adenocarcinoma of Barrett's esophagus

Cited by 25 publications

References 37 publications

c-Ski in health and disease

c-Ski in health and disease

The Oncoprotein c-Ski Functions as a Direct Antagonist of the Transforming Growth Factor-β Type I Receptor

Influence of genetics on tumoral pathologies: The example of the adenocarcinoma arising in Barrett's esophagus

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