Loss of Concurrent Regulation of the Expression of BIF-1, BAX, and Beclin-1 in Primary and Metastatic Melanoma

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Ž. Frangež¹, S. M. Seyed Jafari², R. E. Hunger², and H.-U. Simon^1,3,a*

¹Institute of Pharmacology, University of Bern, 3010 Bern, Switzerland

²Department of Dermatology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland

³Department of Clinical Immunology and Allergology, Sechenov University, 119435 Moscow, Russia

^* To whom correspondence should be addressed.

Received July 8, 2020; Revised July 8, 2020; Accepted July 12, 2020

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Melanoma is one of the most aggressive and drug-resistant cancers. Despite novel promising therapeutic strategies, the prognosis of metastatic melanoma patients remains poor and it is often associated with high relapse rates. Endophilin B1, also known as BIF-1, is a multifunctional protein involved in several biological processes such as autophagy and apoptosis. BIF-1 promotes apoptosis through binding to BAX and its translocation to the mitochondrial outer membrane. On the other hand, BIF-1 can interact with Beclin-1 through UVRAG to promote autophagy. Several reports suggest an ambiguous role of BIF-1 in cancer development and progression. For example, it has been demonstrated that the expression of BIF-1 is reduced in both primary and metastatic melanoma and that the reduction of BIF-1 expression is associated with reduced overall survival of melanoma patients. Here we show that the expression of Beclin-1 and active form of BAX are also reduced in the melanoma patients. However, while we observed strong positive correlations between the expression of BIF-1 and Beclin-1 as well as between BIF-1 and BAX in benign nevi, these correlations were lost in the primary and metastatic melanoma cells. These data indicate disruption in the proximal molecular mechanisms which regulate expression of BIF-1, Beclin-1, and BAX in the primary and metastatic melanoma.

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KEY WORDS: apoptosis, autophagy, BAX, Beclin-1, BIF-1, melanoma

DOI: 10.1134/S0006297920100107

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