BIF-1 inhibits both mitochondrial and glycolytic ATP production: its downregulation promotes melanoma growth.

Frangež, Živa; Fernández-Marrero, Yuniel; Stojkov, Darko; Seyed Jafari, S. Morteza; Hunger, Robert E.; Djonov, Valentin; Riether, Carsten; Simon, Hans-Uwe (2020). BIF-1 inhibits both mitochondrial and glycolytic ATP production: its downregulation promotes melanoma growth. Oncogene, 39(26), pp. 4944-4955. Springer Nature 10.1038/s41388-020-1339-8

[img] Text
Simon_BIF-1 inhabits both mitochondrial and glycolytic ATP production.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (1MB) | Request a copy
[img]
Preview
Text
Simon_BIF-1_Oncogene_suppl..pdf - Accepted Version
Available under License Publisher holds Copyright.

Download (1MB) | Preview

Endophilin B1, also known as BAX-interacting protein 1 (BIF-1), is part of the endophilin B protein family, and is a multifunctional protein involved in the regulation of apoptosis, autophagy, and mitochondrial morphology. The role of BIF-1 in cancer is controversial since previous reports indicated to both tumor-promoting and tumor-suppressive roles, perhaps depending on the cancer cell type. In the present study, we report that BIF-1 is significantly downregulated in both primary and metastatic melanomas, and that patients with high levels of BIF-1 expression exhibited a better overall survival. Depleting BIF-1 using CRISPR/Cas9 technology in melanoma cells resulted in higher proliferation rates both in vitro and in vivo, a finding that was associated with increased ATP production, metabolic acidification, and mitochondrial respiration. We also observed mitochondrial hyperpolarization, but no increase in the mitochondrial content of BIF-1-knockout melanoma cells. In contrast, such knockout melanoma cells were equally sensitive to anticancer drug- or UV irradiation-induced cell death, and exhibited similar autophagic activities as compared with control cells. Taken together, it appears that downregulation of BIF-1 contributes to tumorigenesis in cutaneous melanoma by upregulating mitochondrial respiration and metabolism, independent of its effect on apoptosis and autophagy.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Tumor-Immunologie

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology
09 Interdisciplinary Units > Microscopy Imaging Center (MIC)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Frangez, Ziva, Fernández Marrero, Yuniel, Stojkov, Darko, Jafari, Morteza, Hunger, Robert, Djonov, Valentin Georgiev, Riether, Carsten, Simon, Hans-Uwe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1476-5594

Publisher:

Springer Nature

Language:

English

Submitter:

Celine Joray

Date Deposited:

29 Jun 2020 15:16

Last Modified:

02 Mar 2023 23:33

Publisher DOI:

10.1038/s41388-020-1339-8

PubMed ID:

32493957

BORIS DOI:

10.7892/boris.144913

URI:

https://boris.unibe.ch/id/eprint/144913

Actions (login required)

Edit item Edit item
Provide Feedback