The Oncogene HER2/neu (ERBB2) Requires the Hypoxia-inducible Factor HIF-1 for Mammary Tumor Growth and Anoikis Resistance

Whelan, Kelly A.; Schwab, Luciana P.; Karakashev, Sergey; Franchetti, Lisa; Johannes, Gregg J.; Seagroves, Tiffany N.; Reginato, Mauricio J.

doi:10.1074/jbc.m112.426999

Cited by 70 publications

(62 citation statements)

References 47 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have linked multiple, distinct members of the Bcl-2 family to ERK-mediated inhibition of anoikis (13,27,28,30,(37)(38)(39). Therefore, we looked for differences in the expression of either pro-apoptotic (e.g.…”

Section: Aggregate Formation Facilitates Anoikis Evasion In E-cadherimentioning

confidence: 99%

The Role of Multicellular Aggregation in the Survival of ErbB2-positive Breast Cancer Cells during Extracellular Matrix Detachment

Rayavarapu

Heiden²,

Pagani³

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Cancer cells evade death caused by extracellular matrix (ECM)-detachment to facilitate metastasis. Results: ErbB2-expressing cancer cells form aggregates during ECM-detachment that promote survival signaling through EGFR. Conclusion: Multicellular aggregation in ErbB2 positive cancer cells promotes survival by preventing EGFR degradation. Significance: Disrupting aggregation or inhibiting EGFR may be effective strategies to eliminate ErbB2-expressing cancer cells during ECM-detachment.

show abstract

Section: Aggregate Formation Facilitates Anoikis Evasion In E-cadherimentioning

confidence: 99%

The Role of Multicellular Aggregation in the Survival of ErbB2-positive Breast Cancer Cells during Extracellular Matrix Detachment

Rayavarapu

Heiden²,

Pagani³

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…[18][19][20] Interestingly, previous studies have shown that ErbB2 and EGFR, which are hyperactivated in a substantial percentage of IBC patients, 21 can effectively antagonize the anoikis program to facilitate anchorage-independent growth. [22][23][24][25][26][27][28] However, a detailed examination of the molecular mechanisms underlying anoikis inhibition in IBC cells has yet to be completed. In this study, we demonstrate that signaling from EGFR and ErbB2 through ERK/MAPK has a major role in the ability of IBC cells to survive in the absence of ECM attachment.…”

mentioning

confidence: 99%

Anoikis evasion in inflammatory breast cancer cells is mediated by Bim-EL sequestration

et al. 2014

View full text Add to dashboard Cite

Inflammatory breast cancer (IBC) is a rare and highly invasive type of breast cancer, and patients diagnosed with IBC often face a very poor prognosis. IBC is characterized by the lack of primary tumor formation and the rapid accumulation of cancerous epithelial cells in the dermal lymphatic vessels. Given that normal epithelial cells require attachment to the extracellular matrix (ECM) for survival, a comprehensive examination of the molecular mechanisms underlying IBC cell survival in the lymphatic vessels is of paramount importance to our understanding of IBC pathogenesis. Here we demonstrate that, in contrast to normal mammary epithelial cells, IBC cells evade ECM-detachment-induced apoptosis (anoikis). ErbB2 and EGFR knockdown in KPL-4 and SUM149 cells, respectively, causes decreased colony growth in soft agar and increased caspase activation following ECM detachment. ERK/MAPK signaling was found to operate downstream of ErbB2 and EGFR to protect cells from anoikis by facilitating the formation of a protein complex containing Bim-EL, LC8, and Beclin-1. This complex forms as a result of Bim-EL phosphorylation on serine 59, and thus Bim-EL cannot localize to the mitochondria and cause anoikis. These results reveal a novel mechanism that could be targeted with innovative therapeutics to induce anoikis in IBC cells.

show abstract

“…The less strong effect in increasing mRNA/protein expression of Bid, Bim and Puma induced by the MAPK pathway inhibitor PD98059 might be related with other activating/inhibiting signal pathway like hypoxia-inducible factor-1a (HIF-1a) activated by sevoflurane post-conditioning [2]. Some studies showed that HIF-1a inhibits transcriptions of Bid, Bim and Puma gene that may help cells to adapt to hypoxic/ischemic circumstances [30][31][32][33]. An essential axis of activation of Bid, Bim, Puma-BAX and BAK was correlated with activating the mitochondrial death program, which could offer common ground for therapeutic interventions [8].…”

Section: Discussionmentioning

confidence: 96%

Sevoflurane Post-conditioning Protects Primary Rat Cortical Neurons Against Oxygen–Glucose Deprivation/Resuscitation: Roles of Extracellular Signal-Regulated Kinase 1/2 and Bid, Bim, Puma

Zhang

Xun²,

Jiang³

2015

Neurochem Res

View full text Add to dashboard Cite

Temporal post-conditioning to induce neuroprotection against brain ischemia-reperfusion injury insult is considered to be an effective intervention, but the exact mechanisms of sevoflurane post-conditioning are poorly understood. Extracellular signal-related kinases 1/2 (Erk1/2) play a pivotal role in the cell growth and proliferation. The essential axis of activator Bid, Bim, Puma (BH3s) and BAX, BAK in activating the mitochondrial death program might offer common ground for cell death signal. We hypothesized that, sevoflurane post-conditioning might inhibit the expression of Bid, Bim and Puma and is activated by phosphor-Erk1/2 to reduce neuronal death. To test this hypothesis, we exposed primary cultured cortical neurons to oxygen-glucose deprivation for 1 h and resuscitation for 24 h (OGD/R). The assays of MTT, propidium iodide uptake, JC-1 fluorescence and western blot demonstrated that OGD/R exposure reduced cell viability, increased cell death, decreased mitochondrial membrane potential and the expressions of Bid, Bim, and Puma. Inhibition of Erk1/2 phosphorylation could partially attenuate 2 % of sevoflurane post-conditioning mediated increase in neuronal viability and mitochondrial membrane potential, and also a decrease in cell death and expression of Bid, Bim and Puma after OGD/R treatment. The results demonstrated that, the protection of sevoflurane post-conditioning markedly reducing death of cortical neurons exposed to OGD/R could be correlated with down-regulation of Bid, Bim and Puma expression mediated by phosphorylation/activation of Erk1/2.

show abstract

The Oncogene HER2/neu (ERBB2) Requires the Hypoxia-inducible Factor HIF-1 for Mammary Tumor Growth and Anoikis Resistance

Cited by 70 publications

References 47 publications

The Role of Multicellular Aggregation in the Survival of ErbB2-positive Breast Cancer Cells during Extracellular Matrix Detachment

The Role of Multicellular Aggregation in the Survival of ErbB2-positive Breast Cancer Cells during Extracellular Matrix Detachment

Anoikis evasion in inflammatory breast cancer cells is mediated by Bim-EL sequestration

Sevoflurane Post-conditioning Protects Primary Rat Cortical Neurons Against Oxygen–Glucose Deprivation/Resuscitation: Roles of Extracellular Signal-Regulated Kinase 1/2 and Bid, Bim, Puma

Contact Info

Product

Resources

About