TGF-β signalling pathways in early Xenopus development

Hill, Caroline S.

doi:10.1016/s0959-437x(00)00229-x

Cited by 80 publications

(64 citation statements)

References 76 publications

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“…The levels and the duration of residence in the nucleus of SMAD4 are important events for the response to TGFb in the cells. Consistent with the notion that TGFb can act as a morphogen that induces distinct cell fates along a concentration gradient in embryonic development, many studies demonstrate that the intensity and duration of the TGFb-SMAD response are important determinants for signaling specificity and, therefore, the activity of SMADs is carefully regulated (Gurdon & Bourillot 2001, Hill 2001, ten Dijke & Hill 2004. Enhanced proteasomal degradation of SMAD4 is responsible for TGFb resistance in breast cancer (Dupont et al 2005).…”

Section: Discussionmentioning

confidence: 85%

Role of reduced expression of SMAD4 in papillary thyroid carcinoma

D’Inzeo¹,

Nicolussi²,

A³

et al. 2010

Journal of Molecular Endocrinology

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It has been demonstrated that transforming growth factor-b (TGFb) and other members of TGFb superfamily play an important role in thyroid proliferative diseases. The deficiencies of SMAD4 are responsible to accelerate the malignant progression of neoplastic lesions in several types of tumors. Therefore, the objective of the present study was to determine the functional role of reduced expression of SMAD4 in human papillary thyroid carcinogenesis. For this purpose, we examined the TGFb response in two cell lines, TPC-1 and BCPAP. Our data demonstrated for the first time that these cells showed a strong reduction in the level of SMAD4 protein, which was responsible for an alteration of TGFb signaling and for some of the TGFb-mediated biological effects. The overexpression of SMAD4, restoring TGFb transduction, determined a significant increase of antiproliferative response to TGFb, and reduced the invasive behavior of these cells. Therefore, our data indicated that reduction of SMAD4 may play a significant role in thyroid carcinogenesis.

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Section: Discussionmentioning

confidence: 85%

Role of reduced expression of SMAD4 in papillary thyroid carcinoma

D’Inzeo¹,

Nicolussi²,

A³

et al. 2010

Journal of Molecular Endocrinology

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“…Activin is expressed at the protein level in developing Xenopus laevis embryos (Ariizumi et al, 1991, Fukui et al, 1993, Fukui et al, 1994, Smith et al, 1991. Activin can interact with specific receptors to activate the expression of genes, including Xbrachyury (Xbra), chordin (chd) and cerberus (cer) through the smad2/4 intracellular signaling pathway (Attisano and Wrana, 1998, Bourillot et al, 2002, Bouwmeester et al, 1996, Hill, 2001, Miyazono et al, 2000, Sasai et al, 1994, Smith, 1993, Smith et al, 1991. Treatment with activin induces animal cap cells to differentiate into specific tissues via the expression of tissue-specific genes in a tightly controlled temporal and dose-dependent manner (Ariizumi et al, 1991, Green et al, 1992, Gurdon et al, 1999, Smith, 1993, Smith et al, 1991.…”

Section: Introductionmentioning

confidence: 99%

Comparison of induction during development between Xenopus tropicalis and Xenopus laevis

Sedohara¹,

Suzawa²,

Asashima³

2006

Int. J. Dev. Biol.

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Several in vitro systems exist for the induction of animal caps using growth factors such as activin. In this paper, we compared the competence of activin-treated animal cap cells dissected from the late blastulae of Xenopus tropicalis and Xenopus laevis. The resultant tissue explants from both species differentiated into mesodermal and endodermal tissues in a dosedependent manner. In addition, RT-PCR analysis revealed that organizer and mesoderm markers were expressed in a similar temporal and dose-dependent manner in tissues from both organisms. These results indicate that animal cap cells from Xenopus tropicalis have the same competence in response to activin as those from Xenopus laevis.

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“…The duration of residence in the nucleus of Smad4 is an important event for the response to TGFb in the cells (Pierreux et al 2000, Watanabe et al 2000, Hill 2009). Many studies demonstrate that the strength and the specificity of signaling correlate with the time that Smad complexes spend in the nucleus; therefore, the activity of Smads is carefully regulated (Gurdon & Bourillot 2001, Hill 2001, ten Dijke & Hill 2004, Schmierer et al 2008. Several mechanisms have been suggested; Smad4 nuclear accumulation is dependent on activated R-Smad binding (Liu et al 1997, Hoodless et al 1999, Watanabe et al 2000 or its interaction with CAN/Nup214 via its MH2 domain (Xu et al 2002).…”

Section: Discussionmentioning

confidence: 99%

A novel human Smad4 mutation is involved in papillary thyroid carcinoma progression

D’Inzeo¹,

Nicolussi²,

Donini³

et al. 2011

Endocrine-Related Cancer

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Smad proteins are the key effectors of the transforming growth factor b (TGFb) signaling pathway in mammalian cells. Smad4 plays an important role in human physiology, and its mutations were found with high frequency in wide range of human cancer. In this study, we have functionally characterized Smad4 C324Y mutation, isolated from a nodal metastasis of papillary thyroid carcinoma. We demonstrated that the stable expression of Smad4 C324Y in FRTL-5 cells caused a significant activation of TGFb signaling, responsible for the acquisition of transformed phenotype and invasive behavior. The coexpression of Smad4 C324Y with Smad4 wild-type determined an increase of homo-oligomerization of Smad4 with receptor-regulated Smads and a lengthening of nuclear localization. FRTL-5 clones overexpressing Smad4 C324Y showed a strong reduction of response to antiproliferative action of TGFb1, acquired the ability to grow in anchorageindependent conditions, showed a fibroblast-like appearance and a strong reduction of the level of E-cadherin, one crucial event of the epithelial-mesenchymal transition process. The acquisition of a mesenchymal phenotype gave the characteristics of increased cellular motility and a significant reduction in adhesion to substrates such as fibronectin and laminin. Overall, our results demonstrate that the Smad4 C324Y mutation plays an important role in thyroid carcinogenesis and can be considered as a new prognostic and therapeutic target for thyroid cancer.

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TGF-β signalling pathways in early Xenopus development

Cited by 80 publications

References 76 publications

Role of reduced expression of SMAD4 in papillary thyroid carcinoma

Role of reduced expression of SMAD4 in papillary thyroid carcinoma

Comparison of induction during development between Xenopus tropicalis and Xenopus laevis

A novel human Smad4 mutation is involved in papillary thyroid carcinoma progression

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