Enhanced sensitivity to cytochrome c-induced apoptosis mediated by PHAPI in breast cancer cells

Zachary T. Schafer, Amanda B. Parrish, Kevin Wright, Seth S. Margolis, Jeffrey R. Marks, Mohanish Deshmukh, Sally Kornbluth

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Apoptotic signaling defects both promote tumorigenesis and confound chemotherapy. Typically, chemotherapeutics stimulate cytochrome c release to the cytoplasm, thereby activating the apoptosome. Although cancer cells can be refractory to cytochrome c release, many malignant cells also exhibit defects in cytochrome c-induced apoptosome activation, further promoting chemotherapeutic resistance. We have found that breast cancer cells display an unusual sensitivity to cytochrome c-induced apoptosis when compared with their normal counterparts. This sensitivity, not observed in other cancers, resulted from enhanced recruitment of caspase-9 to the Apaf-1 caspase recruitment domain. Augmented caspase activation was mediated by PHAPI, which is overexpressed in breast cancers. Furthermore, cytochrome c microinjection into mammary epithelial cells preferentially killed malignant cells, suggesting that this phenomenon might be exploited for chemotherapeutic purposes.

Original languageEnglish (US)
Pages (from-to)2210-2218
Number of pages9
JournalCancer Research
Volume66
Issue number4
DOIs
StatePublished - Feb 15 2006
Externally publishedYes

Fingerprint

Cytochromes c
Apoptosis
Breast Neoplasms
Apoptosomes
Caspase 9
Microinjections
Caspases
Neoplasms
Carcinogenesis
Cytoplasm
Breast
Epithelial Cells
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Schafer, Z. T., Parrish, A. B., Wright, K., Margolis, S. S., Marks, J. R., Deshmukh, M., & Kornbluth, S. (2006). Enhanced sensitivity to cytochrome c-induced apoptosis mediated by PHAPI in breast cancer cells. Cancer Research, 66(4), 2210-2218. https://doi.org/10.1158/0008-5472.CAN-05-3923

Enhanced sensitivity to cytochrome c-induced apoptosis mediated by PHAPI in breast cancer cells. / Schafer, Zachary T.; Parrish, Amanda B.; Wright, Kevin; Margolis, Seth S.; Marks, Jeffrey R.; Deshmukh, Mohanish; Kornbluth, Sally.

In: Cancer Research, Vol. 66, No. 4, 15.02.2006, p. 2210-2218.

Research output: Contribution to journalArticle

Schafer, ZT, Parrish, AB, Wright, K, Margolis, SS, Marks, JR, Deshmukh, M & Kornbluth, S 2006, 'Enhanced sensitivity to cytochrome c-induced apoptosis mediated by PHAPI in breast cancer cells', Cancer Research, vol. 66, no. 4, pp. 2210-2218. https://doi.org/10.1158/0008-5472.CAN-05-3923
Schafer, Zachary T. ; Parrish, Amanda B. ; Wright, Kevin ; Margolis, Seth S. ; Marks, Jeffrey R. ; Deshmukh, Mohanish ; Kornbluth, Sally. / Enhanced sensitivity to cytochrome c-induced apoptosis mediated by PHAPI in breast cancer cells. In: Cancer Research. 2006 ; Vol. 66, No. 4. pp. 2210-2218.
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