SMAD4 and its role in pancreatic cancer

Xiang, Xiao; Wu, Weidong; Huang, Chen; Cen, Gang; Jiang, Tao; Cao, Jun; Huang, Kai-Wen; Qiu, Zhengjun

doi:10.1007/s13277-014-2883-z

Cited by 83 publications

(69 citation statements)

References 90 publications

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“…As a member of the TGF-β signaling family, SMAD4 is involved in many cell functions including differentiation, apoptosis, and cell cycle control [68,69]. In human cancers, the SMAD4 gene can be damaged by mutation or LOH or silenced by gene deletion (Table 2 -9).…”

Section: Inactivation Of Smad4 By Mislocalizationmentioning

confidence: 99%

Loss of Tumor Suppressor Gene Function in Human Cancer: An Overview

Wei¹,

Wu²,

Rajasekaran³

et al. 2018

Cell Physiol Biochem

266

142

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Cancer is a disease caused by the accumulation of genetic and epigenetic changes in two types of genes: tumor suppressor genes (TSGs) and proto-oncogenes. Extensive research has been conducted over the last few decades to elucidate the role of TSGs in cancer development. In cancer, loss of TSG function occurs via the deletion or inactivation of two alleles, according to Knudson’s two-hit model hypothesis. It has become clear that mutations in TSGs are recessive at the level of an individual cell; therefore, a single mutation in a TSG is not sufficient to cause carcinogenesis. However, many studies have identified candidate TSGs that do not conform with this standard definition, including genes inactivated by epigenetic silencing rather than by deletion. In addition, proteasomal degradation by ubiquitination, abnormal cellular localization, and transcriptional regulation are also involved in the inactivation of TSGs. This review incorporates these novel additional mechanisms of TSG inactivation into the existing two-hit model and proposes a revised multiple-hit model that will enable the identification of novel TSGs that can be used as prognostic and predictive biomarkers of cancer.

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Section: Inactivation Of Smad4 By Mislocalizationmentioning

confidence: 99%

Loss of Tumor Suppressor Gene Function in Human Cancer: An Overview

Wei¹,

Wu²,

Rajasekaran³

et al. 2018

Cell Physiol Biochem

266

142

View full text Add to dashboard Cite

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“…Smad 2, 3 and 4 proteins have two regions called mad homology 1 and 2 (MH 1 and 2) at the amino (N) and carboxyl (C) terminal ends, respectively 4. The MH1 domain is involved in DNA binding, while MH2 is involved in homodimerisation and heterodimerisation 5.…”

Section: Smad4/dpc4 Structure and Functionmentioning

confidence: 99%

“…Smad4 protein shuttles between the nucleus and cytoplasm4 (figure 1). Nuclear entry of smad4 is independent of TGF-β signalling and occurs as a spontaneous process 4.…”

Section: Location Of Smad4/dpc4 Proteinmentioning

confidence: 99%

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Smad4/DPC4

McCarthy¹,

Chetty²

2018

J Clin Pathol

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Smad4 or DPC4 belongs to a family of signal transduction proteins that are phosphorylated and activated by transmembrane serine-threonine receptor kinases in response to transforming growth factor beta (TGF-β) signaling via several pathways. The gene acts as a tumour suppressor gene and inactivation of smad4/DPC4 is best recognised in pancreatic cancer. However, smad4/DPC4 is also mutated in other conditions and cancers such as juvenile polyposis syndrome with and without hereditary haemorrhagic telangiectasia, colorectal and prostate cancers.Immunohistochemistry for smad4/DPC4 protein is most useful in separating benign/reactive conditions from pancreatic cancer in needle/core biopsies. In normal and reactive states, the protein is localised to the cytoplasm and nucleus, while the protein is lost in high-grade pancreatic intraepithelial neoplasia/carcinoma in situ and pancreatic cancer.

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“…Notably, likewise in CRC, TGF-β signaling is silenced in a large number of tumor pancreatic cancers, particularly by mutations affecting SMAD 4, the mandatory conveyor of RSMADs into the cell (80). In these mutant cells, transport of R-SMADs into the nucleus comes to a standstill.…”

Section: Vitamin D Tgf-β/smad Signaling and Cafs In Colorectal Cancermentioning

confidence: 99%

Vitamin D and Myofibroblasts in Fibrosis and Cancer: At Cross-purposes with TGF-β/SMAD Signaling

Shany

Sigal-Batikoff

Lamprecht

2016

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As mentioned briefly above, one of the principal steps whereby normal stromal fibroblasts acquire the CAF phenotype is their trans-differentiation to myofibroblasts. Notably, we and others (10, 11) have been impressed by the striking similarity in biological behavior and function of the myofibroblast in neoplasia and in a vast range of nonneoplastic chronic diseases that are characterized by extensive 6225 Τhis article is freely accessible online.

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SMAD4 and its role in pancreatic cancer

Cited by 83 publications

References 90 publications

Loss of Tumor Suppressor Gene Function in Human Cancer: An Overview

Loss of Tumor Suppressor Gene Function in Human Cancer: An Overview

Smad4/DPC4

Vitamin D and Myofibroblasts in Fibrosis and Cancer: At Cross-purposes with TGF-β/SMAD Signaling

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