A dynamic podosome-like structure of epithelial cells

Spinardi, Laura; Rietdorf, Jens; Nitsch, Lucio; Bono, Marı́a Rosa; Tacchetti, Carlo; Way, Michael; Marchisio, Pier Carlo

doi:10.1016/j.yexcr.2004.01.007

Cited by 102 publications

(105 citation statements)

References 81 publications

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“…Gelsolin is an actin-regulatory protein coded by chromosome 9q33, a region reported as frequently deleted in bladder cancer. 24 This observation led us to select this target for further validation analyses. Hemidesmosomes are organized around a core of actin filaments that appear early during cell adhesion.…”

Section: Discussionmentioning

confidence: 99%

“…24 Alteration of actin polymerization and/or remodeling plays pivotal role in regulating the morphological and phenotypic events of a malignant cell. 24 The actin remodeling is the result not only of the activation of oncogenic actin signaling pathways (eg, Ras in bladder cancer) but also of the inactivation of several important actin-binding proteins that have tumor suppressive functions (eg, Gelsolin). 9,24 Accumulation of evidence exists to indicate the tumor suppressive functions of actin regulatory proteins.…”

Section: Discussionmentioning

confidence: 99%

“…24 The actin remodeling is the result not only of the activation of oncogenic actin signaling pathways (eg, Ras in bladder cancer) but also of the inactivation of several important actin-binding proteins that have tumor suppressive functions (eg, Gelsolin). 9,24 Accumulation of evidence exists to indicate the tumor suppressive functions of actin regulatory proteins. Gene expression analysis suggests that actin alterations are progressive and that distinctive actin remodeling profiles are associated with different stages of bladder cancer development and progression.…”

Section: Discussionmentioning

confidence: 99%

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Genomic and Proteomic Profiles Reveal the Association of Gelsolin to TP53 Status and Bladder Cancer Progression

Sänchez‐Carbayo

Socci

Richstone

et al. 2007

The American Journal of Pathology

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Bladder cancer transformation and immortalization require the inactivation of key regulatory genes, including TP53. Genotyping of a large cohort of bladder cancer patients (n ‫؍‬ 256) using the TP53 GeneChip showed mutations in 103 cases (40.2%), the majority of them mapping to the DNA-binding core domain. TP53 mutation status was significantly associated with tumor stage (P ‫؍‬ 0.0001) and overall survival for patients with advanced disease (P ‫؍‬ 0.01). Transcript profiling using oligonucleotide arrays was performed on a subset of these cases (n ‫؍‬ 46). Supervised analyses identified genes differentially expressed between invasive bladder tumors with wild-type (n ‫؍‬ 24) and mutated TP53 (n ‫؍‬ 22). Pathway analyses of top-ranked genes supported the central role of TP53 in the functional network of such gene patterns. A proteomic strategy using reverse phase arrays with protein extracts of bladder cancer cell lines validated the association of identified differentially expressed genes, such as gelsolin, to TP53 status. Immunohistochemistry on tissue microarrays (n ‫؍‬ 294) revealed that gelsolin was associated with tumor stage and overall survival, correlating positively with TP53 status in a subset of these patients. This study further reveals that TP53 mutations are frequent events in bladder cancer progression and identified gelsolin related to TP53 status, tumor staging, and clinical outcome by independent high-throughput strategies. (Am J Pathol

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Genomic and Proteomic Profiles Reveal the Association of Gelsolin to TP53 Status and Bladder Cancer Progression

Sänchez‐Carbayo

Socci

Richstone

et al. 2007

The American Journal of Pathology

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“…3). Recent data indicate that podosome formation requires the presence of several specific proteins, such as members of the WASp family, RhoA and Tks5 (3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

SSeCKS/Gravin/AKAP12 Metastasis Suppressor Inhibits Podosome Formation via RhoA- and Cdc42-Dependent Pathways

Gelman

Gao

2006

Molecular Cancer Research

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Podosomes are poorly understood actin-rich structures notably found in cancer cell lines or in v-Src-transformed cells that are thought to facilitate some of the invasive properties involved in tumor metastasis. The enrichment of the Tks5/Fish protein, a v-Src substrate, is required for formation of podosomes. We showed previously that the tetracycline-regulated reexpression of the Src-suppressed C kinase substrate (SSeCKS, also known as Gravin/AKAP12) inhibited variables of v-Src-induced oncogenic growth in NIH3T3, correlating with the induction of normal actin cytoskeletal structures and cell morphology but not with gross inhibition of Src phosphorylation activity in the cell. Here, we show that SSeCKS reexpression at physiologic levels suppresses podosome formation, correlating with decreases in Matrigel invasiveness, whereas there is no effect on total cellular tyrosine phosphorylation or on the phosphorylation of Tks5/Fish.

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“…Podosomes and invadopodia are very important, but probably not solely responsible for invasion related alterations in actin structure and dynamics. Other structures and mechanisms were also suggested to take part in the local modulation of cytoskeletal structures such as contractile forces, the turnover of substrate adhesions and their associated microfilaments that were required for cell invasion (11,12).…”

Section: Introductionmentioning

confidence: 99%

Neoplastic progression of the human breast cancer cell line G3S1 is associated with elevation of cytoskeletal dynamics and upregulation of MT1-MMP

et al. 2010

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Abstract. The newly established breast cancer cell line G3S1, derived from EM-G3 breast cancer progenitors, was analyzed for functional changes related to neoplastic progression manifested by elevated invasiveness and enhanced capability to degrade gelatin. Degradation of gelatin and invasiveness of G3S1 cells was found to be dependent on the activity of matrix proteinases and actin cytoskeletal dynamics. Therefore, the expression and activity of these proteases was compared in G3S1 and EM-G3 cells. Despite enhanced capability of G3S1 cells to degrade gelatin, these cells exhibited lower levels of secreted extracellular matrix degrading proteases than parental EM-G3 cells. However, the expression of membrane-bound MT1-MMP was strongly elevated in G3S1 cells. While the degradation of gelatin was associated with invadopodia-like structures in both EM-G3 and G3S1 cells, the cytoskeletal remodeling dynamics was greatly elevated in G3S1 cells, suggesting that upregulation of MT1-MMP, together with elevation of cytoskeletal remodeling dynamics can effectively cause elevated invasiveness and enhanced matrix degrading capability in G3S1 cells.

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A dynamic podosome-like structure of epithelial cells

Cited by 102 publications

References 81 publications

Genomic and Proteomic Profiles Reveal the Association of Gelsolin to TP53 Status and Bladder Cancer Progression

Genomic and Proteomic Profiles Reveal the Association of Gelsolin to TP53 Status and Bladder Cancer Progression

SSeCKS/Gravin/AKAP12 Metastasis Suppressor Inhibits Podosome Formation via RhoA- and Cdc42-Dependent Pathways

Neoplastic progression of the human breast cancer cell line G3S1 is associated with elevation of cytoskeletal dynamics and upregulation of MT1-MMP

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