Bcl‐2 and Bcl‐xL play important roles in the crosstalk between autophagy and apoptosis

Zhou, Feifan; Yang, Ying; Xing, Da

doi:10.1111/j.1742-4658.2010.07965.x

Cited by 363 publications

(272 citation statements)

References 89 publications

(109 reference statements)

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“…ECM detachment activates the canonical autophagic pathway through ATG6 and ATG8, sustains ATP levels and delays anoikis. The functional players of such integration are Beclin-1, an autophagic protein acknowledged to modulate the anti-apototic role of Bcl-2 and Bcl-XL [73], ROS and ERKs [72]. Autophagy allows epithelial cells to survive given that they re-adhere onto the ECM in a timely fashion, and it is likely a previously unrecognized tool used by circulating cancer cells to survive anoikis, thereby facilitating tumour cell dormancy though nutrient recovery, as well as dissemination of metastases [74].…”

Section: Physiological Protection From Anoikismentioning

confidence: 99%

Anoikis: an emerging hallmark in health and diseases

Taddei

Giannoni

Fiaschi

et al. 2011

The Journal of Pathology

506

404

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Anoikis is a programmed cell death occurring upon cell detachment from the correct extracellular matrix, thus disrupting integrin ligation. It is a critical mechanism in preventing dysplastic cell growth or attachment to an inappropriate matrix. Anoikis prevents detached epithelial cells from colonizing elsewhere and is thus essential for tissue homeostasis and development. As anchorage-independent growth and epithelial-mesenchymal transition, two features associated with anoikis resistance, are crucial steps during tumour progression and metastatic spreading of cancer cells, anoikis deregulation has now evoked particular attention from the scientific community. The aim of this review is to analyse the molecular mechanisms governing both anoikis and anoikis resistance, focusing on their regulation in physiological processes, as well as in several diseases, including metastatic cancers, cardiovascular diseases and diabetes.

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Section: Physiological Protection From Anoikismentioning

confidence: 99%

Anoikis: an emerging hallmark in health and diseases

Taddei

Giannoni

Fiaschi

et al. 2011

The Journal of Pathology

506

404

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“…Since it is well known that autophagy can be suppressed by the binding between BCL2 and BECN1, 8 we determined the effect of EGFR activation on the interaction between BCL2 and BECN1 at an early time point (4 h) and a later time point (72 h) in hypoxia. Immunoprecipitation (IP) on the binding between BCL2 and BECN1 was performed in U87 cells due to that they expressed much higher BCL2 protein level over time in hypoxia than A549 cells (Fig.…”

Section: Egfr Regulates Hypoxia-induced Autophagy and Cell Deathmentioning

confidence: 99%

“…Since EGFR modulates autophagy, 8 we knocked down EGFR and investigated the amount of cell death at later times during hypoxia where EGFR activation was reduced ( Fig. 4A and B).…”

Section: Egfr Regulates Hypoxia-induced Autophagy and Cell Deathmentioning

confidence: 99%

“…Autophagy is regulated by many intracellular proteins such as the components of the MTOR (mechanistic target of rapamycin [serine/threonine kinase]) pathway, [1][2][3][4][5][6] the antiapoptotic BCL2 (B-cell CLL/lymphoma 2) family members, 7,8 and EGFR (epidermal growth factor receptor). [9][10][11][12] EGFR suppresses autophagy in different cell types [12][13][14] through the activation of EGFR which leads to EGFR binding to the autophagy protein BECN1 (Beclin 1, autophagy related) and subsequent tyrosine phosphorylation of BECN1 at multiple sites.…”

Section: Introductionmentioning

confidence: 99%

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Tyrosine kinase receptor EGFR regulates the switch in cancer cells between cell survival and cell death induced by autophagy in hypoxia

et al. 2016

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(2016) Tyrosine kinase receptor EGFR regulates the switch in cancer cells between cell survival and cell death induced by autophagy in hypoxia, Autophagy, 12:6, 1029-1046, DOI: 10.1080/15548627.2016 ABSTRACTAutophagy is an intracellular lysosomal degradation pathway where its primary function is to allow cells to survive under stressful conditions. Autophagy is, however, a double-edge sword that can either promote cell survival or cell death. In cancer, hypoxic regions contribute to poor prognosis due to the ability of cancer cells to adapt to hypoxia in part through autophagy. In contrast, autophagy could contribute to hypoxia induced cell death in cancer cells. In this study, we showed that autophagy increased during hypoxia. At 4 h of hypoxia, autophagy promoted cell survival whereas, after 48 h of hypoxia, autophagy increased cell death. Furthermore, we found that the tyrosine phosphorylation of EGFR (epidermal growth factor receptor) decreased after 16 h in hypoxia. Furthermore, EGFR binding to BECN1 in hypoxia was significantly higher at 4 h compared to 72 h. Knocking down or inhibiting EGFR resulted in an increase in autophagy contributing to increased cell death under hypoxia. In contrast, when EGFR was reactivated by the addition of EGF, the level of autophagy was reduced which led to decreased cell death. Hypoxia led to autophagic degradation of the lipid raft protein CAV1 (caveolin 1) that is known to bind and activate EGFR in a ligand-independent manner during hypoxia. By knocking down CAV1, the amount of EGFR phosphorylation was decreased in hypoxia and amount of autophagy and cell death increased. This indicates that the activation of EGFR plays a critical role in the switch between cell survival and cell death induced by autophagy in hypoxia.

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“…Autophagy promotes cell survival by the degradation of damaged cellular components (Codogno and Meijer 2005), probably as a result of elevated ROS (Scherz-Shouval and Elazar 2011) in the case of cell senescence. Interestingly, there is crosstalk between autophagy and apoptosis pathways (Zhou et al 2011;Xu et al 2013;Lindqvist and Vaux 2014), with particular emphasis on the anti-apoptotic Bcl2 protein family.…”

Section: The Relationship Between Cell Senescence and Immune Ligand Ementioning

confidence: 99%

Cellular senescence: from growth arrest to immunogenic conversion

Burton

Faragher

2015

AGE

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Cellular senescence was first reported in human fibroblasts as a state of stable in vitro growth arrest following extended culture. Since that initial observation, a variety of other phenotypic characteristics have been shown to co-associate with irreversible cell cycle exit in senescent fibroblasts. These include (1) a proinflammatory secretory response, (2) the up-regulation of immune ligands, (3) altered responses to apoptotic stimuli and (4) promiscuous gene expression (stochastic activation of genes possibly as a result of chromatin remodeling). Many features associated with senescent fibroblasts appear to promote conversion to an immunogenic phenotype that facilitates self-elimination by the immune system. Pro-inflammatory cytokines can attract and activate immune cells, the presentation of membrane bound immune ligands allows for specific recognition and promiscuous gene expression may function to generate an array of tissue restricted proteins that could subsequently be processed into peptides for presentation via MHC molecules. However, the phenotypes of senescent cells from different tissues and species are often assumed to be broadly similar to those seen in senescent human fibroblasts, but the data show a more complex picture in which the growth arrest mechanism, tissue of origin and species can all radically modulate this basic pattern. Furthermore, wellestablished triggers of cell senescence are often associated with a DNA damage response (DDR), but this may not be a universal feature of senescent cells. As such, we discuss the role of DNA damage in regulating an immunogenic response in senescent cells, in addition to discussing less established Batypical^senescent states that may occur independent of DNA damage.

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Bcl‐2 and Bcl‐xL play important roles in the crosstalk between autophagy and apoptosis

Cited by 363 publications

References 89 publications

Anoikis: an emerging hallmark in health and diseases

Anoikis: an emerging hallmark in health and diseases

Tyrosine kinase receptor EGFR regulates the switch in cancer cells between cell survival and cell death induced by autophagy in hypoxia

Cellular senescence: from growth arrest to immunogenic conversion

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