Identification of proteolytic fragments from ErbB-2 that induce apoptosis

Tikhomirov, Oleg; Dikov, Mikhail M.; Carpenter, Graham

doi:10.1038/sj.onc.1208534

Cited by 9 publications

(6 citation statements)

References 23 publications

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“…HER2 may also signal for apoptosis following degradation in hormone-sensitive prostate cancer cells (29). However, it is more likely that HER2 itself is not responsible for the mechanism underlying the effect were are observing, as 86% of the group of hormone-sensitive tumors that express high HER2 levels express high levels of two or more family members, and 46% have high expression levels of three or more family members.…”

Section: Discussionmentioning

confidence: 99%

The Role of HER1-HER4 and EGFRvIII in Hormone-Refractory Prostate Cancer

Edwards

Traynor

Munro

et al. 2006

Clinical Cancer Research

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Purpose: The role of the type I receptor tyrosine kinase (HER) family in progression of prostate cancer is controversial. Breast cancer studies show that these receptors should be investigated as a family. The current study investigates expression of HER1-HER4 and EGFRvIII in matched hormone-sensitive and hormone-refractory prostate tumors. Experimental Design: Immunohistochemical analysis was used to investigate protein expression of HER1-HER4, EGFRvIII, and phosphorylated Akt (pAkt) in matched hormone-sensitive and hormone-refractory prostate tumors. Results: Surprisingly, high HER2 membrane expression in hormone-sensitive tumors was associated with an increased time to biochemical relapse (P = 0.0003), and this translated into longer overall survival (P = 0.0021). Consistent with other studies, HER4 membrane expression in hormone-sensitive tumors was associated with longer time to biochemical relapse (P = 0.042), and EGFRvIII membrane expression was associated with shorter time to biochemical relapse (P = 0.015). An increase in pAkt expression was associated with reduced survival (P = 0.0098). Multivariate analysis showed that HER2 was an independent positive predictive marker of time to relapse in hormone-sensitive prostate tumors (P = 0.014). In contrast, high HER2 expression in hormone-refractory tumors was associated with decreased time to death from biochemical relapse (P = 0.039), and EGFRvIII nuclear expression was associated with decreased time to death from biochemical relapse and decreased overall survival (P = 0.02 and P = 0.005). Conclusion:These results suggest that the HER family may have multiple roles in prostate cancer, and that expression of the proteins alone is insufficient to predict the biological response that they may elicit.

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Section: Discussionmentioning

confidence: 99%

The Role of HER1-HER4 and EGFRvIII in Hormone-Refractory Prostate Cancer

Edwards

Traynor

Munro

et al. 2006

Clinical Cancer Research

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“…Some receptors already share some intriguing characteristics with DRs. For example, ErbB2, a receptor tyrosine kinase related to the EGF receptor family, can be cleaved by caspase, and the generated cytosolic fragment triggers apoptosis (Tikhomirov et al, 2005;Strohecker et al, 2008). Interestingly, this fragment contains a BH3-like domain related to the Bcl protein family involved in mitochondrial apoptosis.…”

Section: Future Members Of the Family?mentioning

confidence: 99%

Dependence receptors: a new paradigm in cell signaling and cancer therapy

2010

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Dependence receptors (DRs) now form a family of more than a dozen membrane receptors that are not linked by their structure, but by common functional traits. The most notable is their ability to trigger two opposite signaling pathways: in the presence of ligand, these receptors activate classic signaling pathways implicated in cell survival, migration and differentiation. In the absence of ligand, they do not stay inactive, rather they elicit an apoptotic signal. Thus, cells expressing this kind of receptor are dependent on the presence of ligand in the extracellular environment to survive. This review will recapitulate the increasing data regarding the molecular mechanisms associated with DRs, their potential implication during development, as well as their deregulation during tumorigenesis and, finally, their emergence as new possible therapeutic targets for cancer treatment.

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“…[87][88][89][90] In addition, it has been demonstrated that full-length RET and ALK receptors display proapoptotic properties in the absence of their ligand and upon caspase processing. These receptors are then considered as potential dependence receptors that could also be involved in the regulation of apoptosis in a physiological context.…”

Section: Is Met On the Way To Dependence?mentioning

confidence: 99%

The shadow of death on the MET tyrosine kinase receptor

Tulasne

Foveau

2007

Cell Death Differ

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The MET tyrosine kinase receptor is a high-affinity receptor for hepatocyte growth factor/scatter factor (HGF/SF). HGF/SF-MET system is necessary for embryonic development, and aberrant MET signalling favours tumorigenesis and metastasis. MET is a prototype of tyrosine kinase receptor, which is able to counteract apoptosis through the initiation of a survival signal involving notably the PI3K-Akt pathway. Paradoxically, the MET receptor is also able to promote apoptosis when activated by HGF/SF or independently of ligand stimulation. The molecular mechanisms underlying this uncommon response have been recently investigated and revealed dual antiapoptotic or proapoptotic property of MET according to the cell type or stress conditions. Although the involvement of MET in the regulation of integrated biological responses mostly took into account its efficient antiapoptotic function, its proapoptotic responses could also be important for regulation of the survival/apoptosis balance and play a role during the development or tumour progression.

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Identification of proteolytic fragments from ErbB-2 that induce apoptosis

Cited by 9 publications

References 23 publications

The Role of HER1-HER4 and EGFRvIII in Hormone-Refractory Prostate Cancer

The Role of HER1-HER4 and EGFRvIII in Hormone-Refractory Prostate Cancer

Dependence receptors: a new paradigm in cell signaling and cancer therapy

The shadow of death on the MET tyrosine kinase receptor

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