The Role of Actinin-4 in Bladder Cancer Invasion

Koizumi, Takahiro; Nakatsuji, Hiroyoshi; Fukawa, Tomoya; Avirmed, Shiirevnyamba; Fukumori, Tomoharu; Takahashi, Masayuki; Kanayama, Hiro‐omi

doi:10.1016/j.urology.2009.09.037

Cited by 35 publications

(55 citation statements)

References 13 publications

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“…49 Network with higher score in ΔNp63 experiment was associated with cancer, tumor morphology, cell death, and survival ( Figure 2B). Relevant modulated proteins of this network were: heat shock proteins, structural proteins such as keratins (K1C18), actinin 4 (ACTN4), and actin-binding protein, which is associated with cell motility and cancer metastasis, 50 ezrin (EZR), involved in maintaining the cell cortex, 51 and enzymes, such as CKRB and glucose-6-phosphate isomerase (G6PI, GPI in the network). Interestingly, the main node of the network deduced by the software was Akt, thus underlining similarity with TAp63.…”

Section: Quantitative Proteomics By Stable Isotope Dimethyl Labeling mentioning

confidence: 99%

p63 Isoforms Regulate Metabolism of Cancer Stem Cells

et al. 2014

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p63 is an important regulator of epithelial development expressed in different variants containing (TA) or lacking (ΔN) the N-terminal transactivation domain. The different isoforms regulate stem-cell renewal and differentiation as well as cell senescence. Several studies indicate that p63 isoforms also play a role in cancer development; however, very little is known about the role played by p63 in regulating the cancer stem phenotype. Here we investigate the cellular signals regulated by TAp63 and ΔNp63 in a model of epithelial cancer stem cells. To this end, we used colon cancer stem cells, overexpressing either TAp63 or ΔNp63 isoforms, to carry out a proteomic study by chemical-labeling approach coupled to network analysis. Our results indicate that p63 is implicated in a wide range of biological processes, including metabolism. This was further investigated by a targeted strategy at both protein and metabolite levels. The overall data show that TAp63 overexpressing cells are more glycolytic-active than ΔNp63 cells, indicating that the two isoforms may regulate the key steps of glycolysis in an opposite manner. The mass-spectrometry proteomics data of the study have been deposited to the ProteomeXchange Consortium (http://proteomecentral. proteomexchange.org) via the PRIDE partner repository with data set identifiers PXD000769 and PXD000768.

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Section: Quantitative Proteomics By Stable Isotope Dimethyl Labeling mentioning

confidence: 99%

p63 Isoforms Regulate Metabolism of Cancer Stem Cells

et al. 2014

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“…ACTN4 is an actin-crosslinking protein that promotes filopodia/microspike formation, migration, and metastasis of many cancer types [9–11]. Endogenous MTBP interacted and partially colocalized with ACTN4 [8].…”

Section: Introductionmentioning

confidence: 99%

MTBP inhibits migration and metastasis of hepatocellular carcinoma

Ranjan

Fan

et al. 2015

Clin Exp Metastasis

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Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with increasing incidence. Despite curative surgical resection and advanced chemotherapy, its survival rate remains low. The presence of microvascular invasion and occult metastasis is one of the major causes for this poor outcome. MDM2 Binding Protein (MTBP) has been implicated in the suppression of cell migration and cancer metastasis. However, clinical significance of MTBP, particularly in human cancer, is poorly understood. Specifically, clinical relevance of MTBP in human HCC has never been investigated. Here we demonstrated that expression of MTBP was significantly reduced in human HCC tissues compared to adjacent non-tumor tissues. MTBP expression was negatively correlated with capsular/vascular invasion and lymph node metastasis. Overexpression of MTBP resulted in the suppression of the migratory and metastatic potential of HCC cells, while its downregulation increased the migration. Consistent with the previous report, MTBP endogenously bound to alpha-actinin 4 (ACTN4) and suppressed ACTN4-mediated cell migration in multiple HCC cell lines. However, MTBP also inhibited migratory potential of PLC/PRF/5 HCC cells whose migration was not altered by manipulation of ACTN4 expression. These results suggest that mechanisms behind MTBP-mediated migration suppression may not be limited to the pathway involving ACTN4 in certain cellular contexts. Additionally, as a potential mechanism for reduced MTBP expression in tumors, we found that MTBP expression was increased following the treatment with histone deacetylase inhibitors (HDIs). Our study, for the first time, provides clinical relevance of MTBP in the suppression of HCC metastasis.

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“…We showed here that clinically relevant concentrations of epothilone B inhibited the motility of the most aggressive type of glioma, glioblastoma-multiforme. Impairment of glioblastoma cell motility by epothilone B observed in the present study was due in part to reduced glioblastoma cell adhesion and collapse of the leading edge and stress fibers, as indicated by redistribution of α-actinin 4, an actin-binding protein localized to these cellular structures with an established role in the motility of metastatic breast, colorectal, brain, and ovarian cancers (17)(18)(19)(20)(21). Taken together epothilone B induced aberrations in the leading edge and stress fibers of glioblastoma cells seen here, irrespective of changes in α-actinin 4 protein levels, suggests that the observed effects on glioblastoma cell motility are a consequence of interfering with actin dynamics and actin containing structures and domains.…”

Section: Discussionmentioning

confidence: 69%

“…5A and B) that were dramatically reduced in u87 cells exposed to 25 nM epothilone B (Fig. 5D) and to a lesser of domain structures (leading edge, trailing edges, and stress fibers) in glioblastoma cells rich in actin and actin-binding proteins; we examined if epothilone B promoted changes in subcellular structures (leading edge, trailing edges, and stress fibers) that contain the actin-binding protein α-actinin 4, which functions to bundle actin microfilaments and has an established role in the motility of cancer cells (17)(18)(19)(20)(21). immunofluorescence labeling studies with an antibody that detects α-actinin 4 revealed a pronounced localization of this non-muscle α-actinin isoform in the leading edge (U373, Lnz) and stress fibers (u373, u87, Lnz) of vehicle control treated cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

The microtubule inhibiting agent epothilone B antagonizes glioma cell motility associated with reorganization of the actin-binding protein α-actinin 4

DuBois¹,

Quick

2011

Oncol Rep

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Abstract. Invasion of normal brain tissue by brain tumor cells is a major contributing factor to the recurrence and resistance of clinically diagnosed glioblastomas to therapy (surgery, chemotherapy, radiation). Here, we have assessed the efficacy of the microtubule inhibiting agent epothilone B on glioblastoma cell motility, a prerequisite cellular program of invasive glioblastomas. Using cell migration assays and immunof luorescence techniques we demonstrated that epothilone B abrogated glioblastoma cell motility as a consequence of α-actinin 4 redistristrubiton and the breakdown of cellular structures (leading edge, stress fibers) it is associated with during cell migration. evaluation of the microtubule actin cross linking factor in glioblastoma cells also revealed epothilone B invoked changes in this cytoskeleton cross linking protein, resembling α-actinin 4 changes in response to epothilone B. We have demonstrated in this study that epothilone B antagonizes glioblastoma cell motility due to the disruption of cytoskeleton binding proteins that aide in preserving the structural organization of the cytoskeleton filamentous network. Furthermore, we provide preclincial evidence that epothilone B effects on glioblastomas are not limited to the impairment of dividing tumors cells but that it also targets migratory and invasive glioblastoma cells, suggesting that this agent has potential clinical benefit due to its ability to target divergent cellular programs in the glioblastoma tumor mass.

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The Role of Actinin-4 in Bladder Cancer Invasion

Cited by 35 publications

References 13 publications

p63 Isoforms Regulate Metabolism of Cancer Stem Cells

p63 Isoforms Regulate Metabolism of Cancer Stem Cells

MTBP inhibits migration and metastasis of hepatocellular carcinoma

The microtubule inhibiting agent epothilone B antagonizes glioma cell motility associated with reorganization of the actin-binding protein α-actinin 4

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