Inhibition of the mitochondrial protein OPA1 curtails breast cancer growth
Breast cancer is the most frequent cancer in Belgium. It concerns about 11,000 new cases detected each year. During her postdoc in Italy, Stéphanie Herkenne discovered that the OPA1 protein is overexpressed in breast cancer cases with a poor prognosis of the patients. Furthermore, genetic or pharmacological inhibition of OPA1 reduces proliferation, migration, adhesion and invasion of breast cancer cells in vitro and in vivo.
Although the mitochondrion is the energy powerhouse of the cell, it has many additional functions. Indeed, it has recently been shown that mitochondria are involved in the regulation of cell death, cell differentiation, immune responses or during autophagy. The mitochondria alone can regulate all these functions because it is not a static organelle but is highly dynamic. Indeed, mitochondria are able to fuse and fragment allowing an exchange of mitochondrial material according to the needs of the cell. Mitochondrial fission is regulated by the cytoplasmic protein DRP1 (Dynamin related protein 1) while fusion requires the intervention of several actors such as Mitofusins 1 and 2 as well as OPA1 (Optic Atrophy Protein 1).
Regarding the mechanism, the researchers found that inhibition of OPA1 in breast cancer cells, including triple-negative breast cancer, does not disrupt mitochondrial functions but instead increases the level of miRNAs belonging to the 148/152 family (148a, 148b and 152). The miRNAs are small non-coding RNAs that have the particularity of preventing the expression of different proteins and these three miRNAs have the particularity of being under-expressed during the development of breast cancer. They are also considered to be inhibitors of tumor growth and invasion.
In conclusion, these data show that targeted inhibition of the OPA1 protein reduces the growth of breast cancers and thus names OPA1 as a potential new target for treating breast cancers, and in particular triple-negative breast cancer, which does not respond to other treatments.
Reference
Inhibition of the mitochondrial protein Opa1 curtails breast cancer growth
Margherita Zamberlan # 1 2 , Amandine Boeckx # 3 , Florian Muller 3 , Federica Vinelli 1 2 , Olivier Ek 1 , Caterina Vianello 1 , Emeline Coart 3 , Keitaro Shibata 1 2 , Aurélie Christian 3 , Francesca Grespi 1 2 , Marta Giacomello 1 , Ingrid Struman 3 , Luca Scorrano # 4 5 , Stéphanie Herkenne # 6
J Exp Clin Cancer Res. 2022 Mar 12;41(1):95. doi: 10.1186/s13046-022-02304-6.
