Re-inforcing the cell death army in the fight against breast cancer

Clara R.L. Oudenaarden, Robert A.H. van de Ven, Patrick W.B. Derksen

Research output: Contribution to journalReview articlepeer-review

7 Citations (SciVal)

Abstract

Metastatic breast cancer is responsible for most breast cancer-related deaths. Disseminated cancer cells have developed an intrinsic ability to resist anchorage-dependent apoptosis (anoikis). Anoikis is caused by the absence of cellular adhesion, a process that underpins lumen formation and maintenance during mammary gland development and homeostasis. In healthy cells, anoikis is mostly governed by B-cell lymphoma-2 (BCL2) protein family members. Metastatic cancer cells, however, have often developed autocrine BCL2-dependent resistance mechanisms to counteract anoikis. In this Review, we discuss how a pro-apoptotic subgroup of the BCL2 protein family, known as the BH3-only proteins, controls apoptosis and anoikis during mammary gland homeostasis and to what extent their inhibition confers tumor suppressive functions in metastatic breast cancer. Specifically, the role of the two pro-apoptotic BH3-only proteins BCL2-modifying factor (BMF) and BCL2-interacting mediator of cell death (BIM) will be discussed here. We assess current developments in treatment that focus on mimicking the function of the BH3-only proteins to induce apoptosis, and consider their applicability to restore normal apoptotic responses in anchorageindependent disseminating tumor cells.

Original languageEnglish
Article numberjcs.212563
JournalJournal of Cell Science
Volume131
Issue number16
DOIs
Publication statusPublished - 2018

Subject classification (UKÄ)

  • Cell and Molecular Biology
  • Cancer and Oncology

Keywords

  • Breast cancer
  • Intrinsic apoptosis
  • Metastasis

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