Details
- Autor(en) / Beteiligte
- Titel
- Pro-apoptotic Bax promotes mesenchymal-epithelial transition by binding to respiratory complex-I and antagonizing the malignant actions of pro-survival Bcl-2 proteins
- Ist Teil von
- Cancer letters, 2018-06, Vol.424, p.127-135
- Ort / Verlag
- Ireland: Elsevier B.V
- Erscheinungsjahr
- 2018
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The plasticity of solid tumors between the epithelial and mesenchymal states critically influences their malignant progression and metastasis. The epithelial-mesenchymal transition (EMT), which supports cancer cell invasion and metastasis, is promoted by pro-survival members (e.g., Bcl-2 and Bcl-XL) of the Bcl-2 protein family, which are well-known key apoptosis regulators. We found that Bcl-w, another pro-survival member, promotes EMT by increasing respiratory complex-I activity and reactive oxygen species (ROS) levels. In contrast, pro-apoptotic Bax facilitates mesenchymal-epithelial transition by binding to complex-I, which inhibits complex-I-induced ROS production. Functional antagonism between pro-survival and pro-apoptotic proteins in regulating tumor plasticity was directly confirmed by co-expressing Bax with Bcl-w or Bcl-XL. Therefore, the balance between the functionally opposing Bcl-2 proteins appears to be a critical determinant of cancer cell phenotypes. We further showed that sub-lethal doses of γ-radiation induced EMT by increasing Bcl-XL and Bcl-w levels and complex-I activity. We propose that Bcl-2 proteins and complex-I are potential targets for preventing tumor progression and the malignant actions of radiotherapy. •Respiratory complex-I promotes EMT of cancer cells by generating ROS.•Bax promotes MET of cancer cells by binding to complex-I.•Bcl-w and Bcl-XL antagonize the actions of Bax, promoting EMT.•Complex-I mediates EMT induction in cancer cells that survive radiotherapy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0304-3835eISSN: 1872-7980DOI: 10.1016/j.canlet.2018.03.033Titel-ID: cdi_proquest_miscellaneous_2020480223
- Format
- –
- Schlagworte
- Animals, Apoptosis, Apoptosis Regulatory Proteins - metabolism, Bax protein, Bcl-2 family, Bcl-2 protein, bcl-2-Associated X Protein - metabolism, Bcl-x protein, Breast Neoplasms - metabolism, Breast Neoplasms - pathology, Cancer, Cancer plasticity, Cancer therapies, Cell Line, Tumor, Cell Plasticity, Cell survival, Complex-I, Conflicts of interest, Diabetes, Electron Transport Complex I - metabolism, Epithelial-Mesenchymal Transition, Female, Functional plasticity, Gene Expression Regulation, Neoplastic, Humans, Lung cancer, MCF-7 Cells, Mesenchyme, Metastases, Metastasis, Mice, Neoplasm Transplantation, Plastic properties, Plasticity, Proteins, Proto-Oncogene Proteins c-bcl-2 - metabolism, Radiation, Radiation effects, Radiation therapy, Reactive oxygen species, Reactive Oxygen Species - metabolism, Solid tumors, Survival, Transcription factors, Tumors, γ Radiation