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

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

Research output: Contribution to journalArticle

44 Scopus citations

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Enhanced sensitivity to cytochrome c-induced apoptosis mediated by PHAPI in breast cancer cells'. Together they form a unique fingerprint.

  • Cite this

    Schafer, Z. T., Parrish, A. B., Wright, K. M., 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