Downregulation of Hsp27 (HSPB1) in MCF-7 human breast cancer cells induces upregulation of PTEN

Cayado-Gutiérrez, Niubys; Moncalero, Vera L.; Rosales, Eliana M.; Berón, Walter; Salvatierra, Edgardo; Alvarez-Olmedo, Daiana; Radrizzani, Martı́n; Ciocca, Daniel R.

doi:10.1007/s12192-012-0367-x

Cited by 45 publications

(37 citation statements)

References 21 publications

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“…In addition, HspB1, HspB4 and HspB5 regulate the cellular resistance to apoptotic conditions. Concerning HspB1 (Bruey et al 2000a; Garrido et al 1999; Mehlen et al 1996b; Paul et al 2002), the resistance originates from its interaction with important regulators of the apoptotic pathways, such as: procaspase-3 (Gibert et al 2012; Pandey et al 2000), cytochrome c (Bruey et al 2000a; Paul et al 2002), Daxx (Charette et al 2000), Stat3 (Rocchi et al 2005), eIF4E (Andrieu et al 2010), F-actin (Paul et al 2002), HDAC6 (Gibert et al 2012), Stat2 (Gibert et al 2012), PTEN (Cayado-Gutiérrez et al 2012) and the general cell survival kinase Akt (Rane et al 2001; Rane et al 2003; Wu et al 2007). For example, up modulation of Akt activity by HspB1 induces the phosphorylation inhibition of Forkhead transcription factors (Jomary et al 2006), antagonizes Bax-mediated mitochondrial damages (Havasi et al 2008) and PEA-15 dependent Fas-induced apoptosis (Hayashi et al 2012).…”

Section: Introductionmentioning

confidence: 99%

“…This is based on the recently described interaction of HspB1 with many crucial cell regulators (see Table 1) that are subsequently modulated in their activity and/or half-life. For example, HspB1 can modulate client proteins that are essential to apoptotic cell death as well as tumorigenic and metastatic processes, such as pro-caspase3 (Gibert et al 2012), cytochrome c (Bruey et al 2000a), Daxx (Charette et al 2000), Stat3 (Rocchi et al 2005), HDM2 (O’Callaghan-Sunol et al 2007), eIF4E (Andrieu et al 2010), HDAC6 (Gibert et al 2012), Stat2 (Gibert et al 2012), Akt (Rane et al 2001; Rane et al 2003; Wu et al 2007), Her2 (Kang et al 2008), PTEN (Cayado-Gutiérrez et al 2012), β-catenin (Fanelli et al 2008) and several others (see Table 1). Modulation of the half-life of the client polypeptides is frequent but this is not a general rule since HspB1 can also regulate their enzymatic activities (Charette and Landry 2000; Rane et al 2003) or modifications (Brunet Simioni et al 2009).…”

Section: Introductionmentioning

confidence: 99%

“…In gliomas, SPARC promotes invasion up-regulating the p38 MAPK/MAPKAPK2/Hsp27 signaling pathway which promotes cancer cell survival by up-regulating pAKT (Hsp27 and AKT interact to regulate the activity of each other) (Golembieski et al 2008, Schultz et al 2012, McClung et al 2012). And there is evidence that down regulation of Hsp27 can cause up-regulation of phosphatase and tensin homologue (PTEN) which has tumor suppressor activity as protein tyrosine phosphatase and as phosphatidylinositol phosphate (PIP) phosphatase (negatively regulating the PI3K/Akt signaling pathway) (Cayado-Gutierrez et al 2012). These authors have suggested an interaction between Hsp27 and PTEN.…”

Section: Introductionmentioning

confidence: 99%

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Heat shock proteins and heat shock factor 1 in carcinogenesis and tumor development: an update

2012

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Heat shock proteins (HSP) are a subset of the molecular chaperones, best known for their rapid and abundant induction by stress. HSP genes are activated at the transcriptional level by heat shock transcription factor 1 (HSF1). During the progression of many types of cancer, this heat shock transcriptional regulon becomes co-opted by mechanisms that are currently unclear, although evidently triggered in the emerging tumor cell. Concerted activation of HSF1 and the accumulation of HSPs then participates in many of the traits that permit the malignant phenotype. Thus cancers of many histologies exhibit activated HSF1 and increased HSP levels that may help to deter tumor suppression and evade therapy in the clinic. We review here the extensive work that has been carried out and is still in progress aimed at: (1) understanding the oncogenic mechanisms by which HSP genes are switched on, (2) determining the roles of HSF1 / HSP in malignant transformation and, (3) discovering approaches to therapy based on disrupting the influence of the HSF1 controlled transcriptome in cancer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Heat shock proteins and heat shock factor 1 in carcinogenesis and tumor development: an update

2012

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“…In cancer cells, high expression levels of HspB1 result in its interaction with Akt and PTEN. HspB1 action towards Akt kinase activity and the stimulation of the degradation of the phosphatase PTEN stimulate the PI3K/Akt signaling pathway and thus enhance the survival of these pathological cells (Cayado-Gutierrez et al 2012 ;Rane et al 2003 ;Wu et al 2007 ). An interesting survival pathway also modulated by HspB1 is the PEA-15 molecular switch linking cell proliferation to Fasinduced apoptosis.…”

Section: Stimulation Of Cell Survival Pathways Senescencementioning

confidence: 99%

Immense Cellular Implications Associated to Small Stress Proteins Expression: Impacts on Human Pathologies

Arrigo

Ducarouge

Lavial

et al. 2015

Heat Shock Proteins

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In addition to being potent chaperones that protect cells against the accumulation of unfolded proteins under stress conditions, mammalian small heat shock proteins (small Hsps) regulate many vital cellular processes in normal and pathological cells. Indeed, these Hsps are constitutively expressed in many tissues and show dramatic changes in their levels of expression in most human pathologies. They are characterized by a large spectrum of activities and are particularly active in protein conformational and infl ammatory diseases as well as in cancer pathologies. It is now believed that the immense cellular implications of small Hsps results from their ability to interact, through particular structural changes, with many different client proteins that are subsequently modulated in their activities or half-lifes. Here, we have integrated functionally and structurally the recent data in the literature concerning the interactions of mammalian small Hsps with specifi c clients. Further analysis with geneMANIA software and database confi rmed the incredibly large number of functions associated with these Hsps. The consequences for human pathologies as well as putative therapeutic strategies are discussed, particularly when the expression of small Hsps is harmful (as in some cancer pathologies) or when it appears benefi cial for patients.

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“…Activated Akt is a well-established survival factor, exerting anti-apoptotic activity by preventing the release of cytochrome C from mitochondria and inactivating Forkhead transcription factors (FKHR), which are known to induce the expression of genes that are critical for apoptosis (Fukunaga and Shioda 2009;Fiandalo and Kyprianou 2012). We have recent evidence to indicate that the down-regulation of Hsp27 (HSPB1) in MCF-7 human breast cancer cells induces upregulation of PTEN and reduces p-Akt levels (Cayado-Gutiérrez et al 2012).…”

Section: Introductionmentioning

confidence: 99%

In MMTV-Her-2/neu transgenic mammary tumors the absence of caveolin-1−/− alters PTEN and NHERF1 but not β-catenin expression

Cuello-Carrión

Cayado-Gutiérrez

Natoli

et al. 2013

Cell Stress and Chaperones

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In a recent study, we have shown that in mammary tumors from mice lacking the Cav-1 gene, there are alterations in specific heat shock proteins as well as in tumor development. With this in mind, we have now investigated other proteins in the same mammary mouse tumor model (Her-2/neu expressing mammary tumors from Cav-1 wild type and Cav-1 null mice), to further comprehend the complex tumor-stroma mechanisms involved in regulating stress responses during tumor development. In this tumor model the cancer cells always lacked of Cav-1, so the KO influenced the Cav-1 in the stroma. By immunohistochemistry, we have found a striking co-expression of β-catenin and Her-2/neu in the tumor cells. The absence of Cav-1 in the tumor stroma had no effect on expression or localization of β-catenin and Her-2/neu. Both proteins appeared co-localized at the cell surface during tumor development and progression. Since Her-2/neu activation induces MTA1, we next evaluated MTA1 in the mouse tumors. Although this protein was found in numerous nuclei, the absence of Cav-1 did not alter its expression level. In contrast, significantly more PTEN protein was noted in the tumors lacking Cav-1 in the stroma, with the protein localized mainly in the nuclei. P-Akt levels were relatively low in tumors from both Cav-1 WT and Cav-1 KO mice. There was also an increase in nuclear NHERF1 expression levels in the tumors arising from Cav-1 KO mice. The data obtained in the MMTV-neu model are consistent with a role for Cav-1 in adjacent breast cancer stromal cells in modulating the expression and localization of important proteins implicated in tumor cell behavior.

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Downregulation of Hsp27 (HSPB1) in MCF-7 human breast cancer cells induces upregulation of PTEN

Cited by 45 publications

References 21 publications

Heat shock proteins and heat shock factor 1 in carcinogenesis and tumor development: an update

Heat shock proteins and heat shock factor 1 in carcinogenesis and tumor development: an update

Immense Cellular Implications Associated to Small Stress Proteins Expression: Impacts on Human Pathologies

In MMTV-Her-2/neu transgenic mammary tumors the absence of caveolin-1−/− alters PTEN and NHERF1 but not β-catenin expression

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