FGF signaling antagonizes cytokine-mediated repression of Sox9 in SW1353 chondrosarcoma cells

Schaefer, Jean; Millham, Michele L.; Crombrugghe, Benoít de; Buckbinder, Leonard

doi:10.1016/s1063-4584(02)00354-0

Cited by 57 publications

(33 citation statements)

References 41 publications

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“…TGF-␤ signaling is a major influence in promoting HSC activation and subsequent COL1 expression; fibroblast growth factor 2 augments ECM deposition (29,45,46). We showed that TGF-␤ increased SOX9 expression in two HSC models, similar to observations in developing chondrocytes (47); previously, fibroblast growth factor 2 increased both SOX9 transcripts and protein in a chondrosarcoma cell line (48). Moreover, both TGF-␤ and fibroblast growth factor 2 promote epithelial-tomesenchymal transition (EMT), whereby quiescent epithelial cells morph into myofibroblast-like cells characterized by ␣-SMA.…”

Section: Discussionsupporting

confidence: 80%

Ectopic SOX9 Mediates Extracellular Matrix Deposition Characteristic of Organ Fibrosis

Hanley

Oakley

Sugden

et al. 2008

Journal of Biological Chemistry

102

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Appropriate temporospatial expression of the transcription factor SOX9 is important for normal development of a wide range of organs. Here, we show that when SOX9 is expressed ectopically, target genes become expressed that are associated with disease. Histone deacetylase inhibitors in clinical trials for cancer therapy induced SOX9 expression via enhanced recruitment of nuclear factor Y (NF-Y) to CCAAT elements in the SOX9 proximal promoter. The effect of histone deacetylase inhibitors could be elicited in cells that normally lack SOX9, such as hepatocytes. In human fetal hepatocytes, this aberrant induction of SOX9 protein caused ectopic expression of COL2A1 and COMP1 that encode extracellular matrix (ECM) components normally associated with chondrogenesis. Previously, ectopic expression of this "chondrogenic" profile has been implicated in vascular calcification. More broadly, inappropriate ECM deposition is a hallmark of fibrosis. We demonstrated that induction of SOX9 expression also occurred during activation of fibrogenic cells from the adult liver when the transcription factor was responsible for expression of the major component of fibrotic ECM, type 1 collagen. These combined data identify new aspects in the regulation of SOX9 expression. They support a role for SOX9 beyond normal development as a transcriptional regulator in the pathology of fibrosis.

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Section: Discussionsupporting

confidence: 80%

Ectopic SOX9 Mediates Extracellular Matrix Deposition Characteristic of Organ Fibrosis

Hanley

Oakley

Sugden

et al. 2008

Journal of Biological Chemistry

102

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“…As cellular models we used HEK293 human embryonic kidney cells (56) and SW1353 human humeral bone chondroblast cells (45). SW1353 cells do not express paralogy group 13 and the majority of other Hox genes (V. Salsi and V. Zappavigna, unpublished results), and conserve many of the signaling pathways of primary chondrocytes (53). Conversely, HEK293 cells express HOXD13 endogenously (see Fig.…”

Section: Resultsmentioning

confidence: 99%

HOXD13 Binds DNA Replication Origins To Promote Origin Licensing and Is Inhibited by Geminin

Salsi¹,

Ferrari²,

Ferraresi

et al. 2009

Molecular and Cellular Biology

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HOX DNA-binding proteins control patterning during development by regulating processes such as cell aggregation and proliferation. Recently, a possible involvement of HOX proteins in replication origin activity was suggested by results showing that a number of HOX proteins interact with the DNA replication licensing regulator geminin and bind a characterized human origin of replication. The functional significance of these observations, however, remained unclear. We show that HOXD13, HOXD11, and HOXA13 bind in vivo all characterized human replication origins tested. We furthermore show that HOXD13 interacts with the CDC6 loading factor, promotes pre-replication complex (pre-RC) proteins assembly at origins, and stimulates DNA synthesis in an in vivo replication assay. HOXD13 expression in cultured cells accelerates DNA synthesis initiation in correlation with the earlier pre-RC recruitment onto origins during G 1 phase. Geminin, which interacts with HOXD13 as well, blocks HOXD13-mediated assembly of pre-RC proteins and inhibits HOXD13-induced DNA replication. Our results uncover a function for Hox proteins in the regulation of replication origin activity and reveal an unforeseen role for the inhibition of HOX protein activity by geminin in the context of replication origin licensing.Hox proteins belong to the large family of homeodomaincontaining DNA-binding proteins. During embryonic development they control cell fates, eventually leading to the generation of different regional identities along the primary body and limb axes (17,35). Genetic analyses, including loss-and gainof-function experiments, showed that vertebrate Hox genes modulate morphogenetic processes by controlling crucial aspects such as cell proliferation and aggregation (16). This is particularly true of 5Ј HoxA and HoxD genes, which are involved in limb patterning (reviewed in references 49 and 65). The inactivation of the Hoxd13 gene in mice, for instance, causes a phenotype resulting from defects in the proliferation and/or condensation of limb mesenchymal cells (11,14).Hox proteins have been shown to act as transcription factors, which are thought to regulate sets of target genes by binding to specific DNA sequences within the transcriptional regulatory regions of these (7,33,38,43,50,51,61,62). Recent findings, however, have hinted at a possible additional function for this family of DNA-binding proteins. Hox proteins have been found to associate with the DNA replication licensing regulator geminin (39), and a number of them have been shown to bind the human LaminB2 and other origins of replication, suggesting their possible role in origin definition and/or assembly of the replication machinery (9,13,20). The functional significance of these observations, however, remained elusive.Origins of replication are poorly defined in metazoa. A consensus sequence appears not to be required for replication initiation in human cells, and only a few origins where replication initiates from a localized site in each cell cycle have been well characterize...

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“…SW1353 cells as well as other chondrocytic tumor cells, including OUMS-27 and HCS-2/8, have been used in many studies as a reliable substitute for primary human chondrocytes. They represent a useful tool with which to investigate the expression of cartilage matrix proteins (17,18), proinflammatory cytokines (19,20), MMP (19,(21)(22)(23)(24), TIMP (18) and chondrocytic transcription factor expression (20,25,26). In a recent publication, comparison of SW1353 cells to primary chondrocytes was described with respect to their gene expression profile and IL-1 responsiveness (27).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-10 does not affect IL-1-induced interleukin-6 and metalloproteinase production in human chondrosarcoma cells, SW1353

Radons¹,

Falk²,

Schubert³

2006

Int J Mol Med

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FGF signaling antagonizes cytokine-mediated repression of Sox9 in SW1353 chondrosarcoma cells

Cited by 57 publications

References 41 publications

Ectopic SOX9 Mediates Extracellular Matrix Deposition Characteristic of Organ Fibrosis

Ectopic SOX9 Mediates Extracellular Matrix Deposition Characteristic of Organ Fibrosis

HOXD13 Binds DNA Replication Origins To Promote Origin Licensing and Is Inhibited by Geminin

Interleukin-10 does not affect IL-1-induced interleukin-6 and metalloproteinase production in human chondrosarcoma cells, SW1353

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