Inhibitory effect of HGF on invasiveness of aggressive MDA-MB231 breast carcinoma cells, and role of HDACs

Ridolfi, Elisa; Matteucci, Emanuela; Maroni, Paola; Desiderio, Maria Alfonsina

doi:10.1038/sj.bjc.6604726

Cited by 23 publications

(12 citation statements)

References 62 publications

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“…*indicates significant difference to the controls (d) participates in lowering chemoinvasion induced by HDAC inhibition [34]. Studies on PC-3 cells underscored a novel mechanism of HDAC-inhibitors by deregulating Akt through disrupting HDAC-protein phosphatase 1 (PP1) complexes [35]. Integrin driven cell adhesion in turn was shown to be sensitive to PP1 [36].…”

Section: Discussionmentioning

confidence: 99%

Impact of combined HDAC and mTOR inhibition on adhesion, migration and invasion of prostate cancer cells

Wedel

Hudak

Seibel

et al. 2011

Clin Exp Metastasis

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The concept of molecular tumor targeting might provide new hope in the treatment of advanced prostate cancer. We evaluated metastasis blocking properties of the histone deacetylase (HDAC) inhibitor valproic acid (VPA) and the mammalian target of rapamycin (mTOR) inhibitor RAD001 on prostate cancer cell lines. RAD001 or VPA were applied to PC-3 or LNCaP cells, either separately or in combination. Adhesion to vascular endothelium or to immobilized collagen, fibronectin or laminin was quantified. Migration and invasion were explored by a modified Boyden chamber assay. Integrin α and β subtypes were analyzed by flow cytometry, western blotting and RT-PCR. Effects of drug treatment on integrin related signaling, Akt and p70S6kinase activation, histone H3 and H4 acetylation were also determined. Separate application of RAD001 or VPA distinctly reduced tumor cell adhesion, migration and invasion, accompanied by elevated Akt activation and p70S6kinase de-activation. Integrin subtype expression was altered significantly by both compounds (VPA > RAD001). When both drugs were used in concert additive effects were observed on the migratory and invasive behavior but not on tumor-endothelium and tumor-matrix interaction. Separate mTOR or HDAC inhibition slows processes related to tumor metastasis. The RAD001-VPA combination showed advantage over VPA monotreatment with particular respect to migration and invasion. Ongoing studies are required to assess the relevance of VPA monotherapy versus VPA-RAD001 combination on tumor cell motility.

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Section: Discussionmentioning

confidence: 99%

Impact of combined HDAC and mTOR inhibition on adhesion, migration and invasion of prostate cancer cells

Wedel

Hudak

Seibel

et al. 2011

Clin Exp Metastasis

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“…Colburn [2,3], or 5-Ets-1 consensus sequences [10]. The expression vector (200 ng) for HIF-1α or HIF-1β (L. Poellinger, Karolinska Institute, Stockholm, Sweden) was co-transfected with the genereporters.…”

Section: Plasmids and Cell Transfectionmentioning

confidence: 99%

“…Cells exposed to hypoxia alone were not starved. COX-2-reporter plasmid (-1432/+59)Luc or (-327/+59)Luc (S. Wilkinson, Vanderbilt University, Nashville, TN) was co-transfected with expression vectors for the dominant negative of ARNT (corresponding to mutated HIF-1 subunit), Jun (TAM67) or Ets-1 (EBHHB) [3,10], or treated with 50 g/ml SN50 (NF-kB inhibitor) or 10 M CGP049090 (TCF-inhibitor) [28,29]. As internal control, Renilla luciferase plasmid was co-transfected, and Firefly/Renilla luciferase activity ratios were calculated by the software.…”

Section: Plasmids and Cell Transfectionmentioning

confidence: 99%

“…Thus, the gene signature associated with poor prognosis facilitates the emergence of metastatic cells in the primary tumor, but the specific set of genes associated with bone metastasis seems responsible for the cellular activities necessary for metastatisation [6][7][8]. For completeness, the metastatic capacity might be considered as a late, acquired event in tumorigenesis and during secondary growth, through epigenetic control of transcription [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Nuclear co-localization and functional interaction of COX-2 and HIF-1α characterize bone metastasis of human breast carcinoma

Maroni

Matteucci²,

Luzzati³

et al. 2010

Breast Cancer Res Treat

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The aim of the present paper was to identify nuclear co-localization of COX-2 and HIF-1α in human-bone metastasis of breast cancer, index of transcriptionally-activated cells and functional for gene expression. In particular, we verified whether hypoxia exerted a direct role on metastasis-gene expression or through COX-2 signaling, due to the relevance for clinical implications to individuate molecular targets for diagnosis and therapy. The experiments were performed in vitro with two autoregulatory loops triggered a specific array of transcription factors responsible for COX-2 transactivation. The novelty was that HGF and TGF-β1 biological signals were produced by hypoxic metastatic cells and, therefore, the microenvironment seemed to be modified by metastaticcell engraftment in the bone. In agreement, HIF-1α expression in bone-marrow supportive cells occurred in metastasis-bearing animals. Altogether, the data supported the pre-metastatic-niche theory. Our observations might be useful to design therapies against bone metastasis, by affecting the phenotype changes of metastatic cells occurring at the secondary growth site through COX-2-HIF-1 interaction.Keywords bone microenvironment · bone metastasis · breast cancer · COX-2 · HIF-1 3

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“…Transfected cells and TGF-β1-treated cells were harvested, resuspended in medium without serum, added (8 × 10 4 per well) in triplicate to the upper chambers, and allowed to invade through Matrigel in the absence of serum. The cells that had invaded the lower surface of the membrane were fixed and stained (63).…”

Section: Matrigel Invasion Assaymentioning

confidence: 99%

NF-κB Activation, Dependent on Acetylation/Deacetylation, Contributes to HIF-1 Activity and Migration of Bone Metastatic Breast Carcinoma Cells

Bendinelli

Matteucci

Maroni

et al. 2009

Molecular Cancer Research

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Here, we show that NF-κB-HIF-1 interaction contributed to breast cancer metastatic capacity by means of an incomplete epithelial/mesenchymal transition and influencing migration, as shown in 1833 (human) and 4T1 (mouse) metastatic cells after different stimuli. The 1833 and the transforming growth factor-β1-exposed 4T1 cells showed both epithelial (E-cadherins) and mesenchymal (N-cadherins and vimentin) markers, and common mechanisms contributed to the retention of certain epithelial characteristics and the control of migration. The complex NF-κB-HIF-1 reciprocal regulation and the enhanced c-Jun expression played a functional role in exacerbating the invasiveness of 1833 cells after p50/p65 transfection and of 4T1 cells exposed to transforming growth factor-β1. Twist expression seemed to exert a permissive role also regulating epithelial/mesenchymal transition markers. After c-Src wild-type (Srcwt) transfection, c-Src-signal transducer overexpression in 1833 cells increased HIF-1 transactivating activity and invasiveness, and changed E-cadherin/N-cadherin ratio versus mesenchymal phenotype. The transcription factor pattern and the motile phenotype of metastatic 1833 cells were influenced by p65-lysine acetylation and HDAC-dependent epigenetic mechanisms, which positively regulated basal NF-κB and HIF-1 activities. However, HDAC3 acted as a corepressor of NF-κB activity in parental MDA-MB231 cells, thus explaining many differences from the derived 1833 clone, including reduced HIF-1α and c-Jun expression. Invasiveness was differently affected by HDAC knockdown in 1833 and MDA-MB231 cells. We suggest that acetylation/deacetylation are critical in establishing the bone-metastatic gene signature of 1833 cells by regulating the activity of NF-κB and HIF-1, and further clarify the epigenetic control of transcription factor network in the motile phenotype of 1833

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Inhibitory effect of HGF on invasiveness of aggressive MDA-MB231 breast carcinoma cells, and role of HDACs

Cited by 23 publications

References 62 publications

Impact of combined HDAC and mTOR inhibition on adhesion, migration and invasion of prostate cancer cells

Impact of combined HDAC and mTOR inhibition on adhesion, migration and invasion of prostate cancer cells

Nuclear co-localization and functional interaction of COX-2 and HIF-1α characterize bone metastasis of human breast carcinoma

NF-κB Activation, Dependent on Acetylation/Deacetylation, Contributes to HIF-1 Activity and Migration of Bone Metastatic Breast Carcinoma Cells

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