BAG3 controls angiogenesis through regulation of ERK phosphorylation

Falco, Antonia; Festa, Michela; Basile, Anna; Rosati, Alessandra; Pascale, Maria; Florenzano, Fulvio; Nori, Stefania Lucia; Nicolin, Vanessa; Benedetto, Maria; Vecchione, Maria Luisa; Arra, Claudio; Barbieri, Antônio; Laurenzi, Vincenzo De; Turco, Maria Caterina

doi:10.1038/onc.2012.17

Cited by 44 publications

(51 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] Moreover, BAG3 regulated angiogenesis of HCC cells through ERK phosphorylation, in accordance with previous studies. 12 Earlier work showed that autophagy-related genes could downregulate angiogenesis; 18,19 however, in our study, knockdown of BAG3 could downregulate the autophagy process. According to these data, a possible molecular In conclusion, we demonstrated that BAG3 knockdown is associated with the invasiveness of HCC cells, potentially by inhibiting EMT and angiogenesis.…”

Section: Bag3 Function In Human Hepatocellular Carcinomacontrasting

confidence: 45%

“…This finding is in accordance with previous studies in glioblastoma and thyroid carcinoma. 10,34 A potential mechanism is that BAG3 knockdown may decrease the tumor neovascularization that supplies the tumor cells with nutrients, 12 thereby inhibiting the tumorigenicity and metastasis of HCC cell lines in vivo. In the current study, we measured CD34 and VEGF expression in vivo.…”

Section: Bag3 Function In Human Hepatocellular Carcinomamentioning

confidence: 99%

See 1 more Smart Citation

BAG3 regulates epithelial–mesenchymal transition and angiogenesis in human hepatocellular carcinoma

Xiao

Cheng

Tong

et al. 2014

Laboratory Investigation

View full text Add to dashboard Cite

Bcl2-associated athanogene 3 (BAG3) protein is a co-chaperone of heat-shock protein (Hsp) 70 and may regulate major physiological and pathophysiological processes. However, few reports have examined the role of BAG3 in human hepatocellular carcinoma (HCC). In this study, we show that BAG3 regulates epithelial-mesenchymal transition (EMT) and angiogenesis in HCC. BAG3 was overexpressed in HCC tissues and cell lines. BAG3 knockdown resulted in reduction in migration and invasion of HCC cells, which was linked to reversion of EMT by increasing E-cadherin expression and decreasing N-cadherin, vimentin and slug expression, as well as suppressing matrix metalloproteinase 2 (MMP-2) expression. In a xenograft tumorigenicity model, BAG3 knockdown effectively inhibited tumor growth and metastasis through reduction in CD34 and VEGF expression and reversal of the EMT pathway. In conclusion, BAG3 is associated with the invasiveness and angiogenesis in HCC, and the BAG3 gene may be a novel therapeutic approach against HCC.

show abstract

Section: Bag3 Function In Human Hepatocellular Carcinomacontrasting

confidence: 45%

Section: Bag3 Function In Human Hepatocellular Carcinomamentioning

confidence: 99%

BAG3 regulates epithelial–mesenchymal transition and angiogenesis in human hepatocellular carcinoma

Xiao

Cheng

Tong

et al. 2014

Laboratory Investigation

View full text Add to dashboard Cite

show abstract

“…ERK1/2 binds to MVP, suggesting that vaults may serve as signaling scaffolds for ERK1/2 or in the transport of phospho-ERK1/2 to the nucleus (40). Bag3 has being shown to stabilize the interaction of ERK1/2 with Dual-specificity Phosphatase 1 in HUVECs and in this case, its removal resulted in G1 block not apoptosis implying its role is cell dependent (41). Our results suggest that MVP and Bag3 promote resistance to apoptosis in senescent cells by promoting or sustaining activation of ERK1/2.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis Reveals a Role for Bcl2-associated Athanogene 3 and Major Vault Protein in Resistance to Apoptosis in Senescent Cells by Regulating ERK1/2 Activation

Pasillas

Shields

Reilly

et al. 2015

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Senescence is a prominent solid tumor response to therapy in which cells avoid apoptosis and instead enter into prolonged cell cycle arrest. We applied a quantitative proteomics screen to identify signals that lead to therapyinduced senescence and discovered that Bcl2-associated athanogene 3 (Bag3) is up-regulated after adriamycin treatment in MCF7 cells. Bag3 is a member of the BAG family of co-chaperones that interacts with Hsp70. Bag3 also regulates major cell-signaling pathways. Mass spectrometry analysis of the Bag3 Complex revealed a novel interaction between Bag3 and Major Vault Protein (MVP).Silencing of Bag3 or MVP shifts the cellular response to adriamycin to favor apoptosis. We demonstrate that Bag3 and MVP contribute to apoptosis resistance in therapyinduced senescence by increasing the level of activation of extracellular signal-regulated kinase1/2 (ERK1/2). Silencing of either Bag3 or MVP decreased ERK1/2 activation and promoted apoptosis in adriamycin-treated cells. An increase in nuclear accumulation of MVP is observed during therapy-induced senescence and the shift in MVP subcellular localization is Bag3-dependent. We propose a model in which Bag3 binds to MVP and facilitates MVP accumulation in the nucleus, which sustains ERK1/2 activation. We confirmed that silencing of Bag3 or MVP shifts the response toward apoptosis and regulates ERK1/2 activation in a panel of diverse breast cancer cell lines. This study highlights Bag3-MVP as an important complex that regulates a potent prosurvival signaling pathway and contributes to chemotherapy resistance in breast cancer.

show abstract

“…Recent studies have suggested a broader role for BAG3. For example, BAG3 regulates epithelial-mesenchymal transition and angiogenesis through ERK phosphorylation [57, 107]; induces epithelial-mesenchymal transition through activation of the transcription factor ZEB1 [108]; and modulates the activity of the transcription factors FoxM1 and Hif1α, the translation regulator HuR and the cell cycle regulators p21 and survivin [109]. BAG3 also downregulates the microRNA-29b which leads to upregulation of the anti-apoptosis protein Mcl-l leading to resistance to anticancer drugs [110].…”

Section: Autophagy and Apoptosismentioning

confidence: 99%

BAG3: a new player in the heart failure paradigm

et al. 2015

View full text Add to dashboard Cite

BAG3 is a cellular protein that is expressed predominantly in skeletal and cardiac muscle but can also be found in the brain and in the peripheral nervous system. BAG3 functions in the cell include: serving as a co-chaperone with members of the heat-shock protein family of proteins to facilitate the removal of misfolded and degraded proteins, inhibiting apoptosis by interacting with Bcl2 and maintaining the structural integrity of the Z-disk in muscle by binding with CapZ. The importance of BAG3 in the homeostasis of myocytes and its role in the development of heart failure was evidenced by the finding that single allelic mutations in BAG3 were associated with familial dilated cardiomyopathy. Furthermore, significant decreases in the level of BAG3 have been found in end-stage failing human heart and in animal models of heart failure including mice with heart failure secondary to trans-aortic banding and in pigs after myocardial infarction. Thus, it becomes relevant to understand the cellular biology and molecular regulation of BAG3 expression in order to design new therapies for the treatment of patients with both hereditary and non-hereditary forms of dilated cardiomyopathy.

show abstract

BAG3 controls angiogenesis through regulation of ERK phosphorylation

Cited by 44 publications

References 41 publications

BAG3 regulates epithelial–mesenchymal transition and angiogenesis in human hepatocellular carcinoma

BAG3 regulates epithelial–mesenchymal transition and angiogenesis in human hepatocellular carcinoma

Proteomic Analysis Reveals a Role for Bcl2-associated Athanogene 3 and Major Vault Protein in Resistance to Apoptosis in Senescent Cells by Regulating ERK1/2 Activation

BAG3: a new player in the heart failure paradigm

Contact Info

Product

Resources

About