1. POTEE promotes breast cancer cell malignancy by inducing invadopodia formation through the activation of SUMOylated Rac1.
- Author
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Martínez-López A, García-Casas A, Infante G, González-Fernández M, Salvador N, Lorente M, Mendiburu-Eliçabe M, Gonzalez-Moreno S, Villarejo-Campos P, Velasco G, Malliri A, and Castillo-Lluva S
- Subjects
- Humans, Female, Signal Transduction, rac1 GTP-Binding Protein metabolism, Cell Movement, Cell Line, Tumor, Podosomes metabolism, Breast Neoplasms
- Abstract
The small GTPase Rac1 (Ras-related C3 botulinum toxin substrate 1) has been implicated in cancer progression and in the poor prognosis of various types of tumors. Rac1 SUMOylation occurs during epithelial-mesenchymal transition (EMT), and it is required for tumor cell migration and invasion. Here we identify POTEE (POTE Ankyrin domain family member E) as a novel Rac1-SUMO1 effector involved in breast cancer malignancy that controls invadopodium formation through the activation of Rac1-SUMO1. POTEE activates Rac1 in the invadopodium by recruiting TRIO-GEF (triple functional domain protein), and it induces tumor cell proliferation and metastasis in vitro and in vivo. We found that the co-localization of POTEE with Rac1 is correlated with more aggressive breast cancer subtypes. Given its role in tumor dissemination, the leading cause of cancer-related deaths, POTEE could represent a potential therapeutic target for these types of cancer., (© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
- Published
- 2024
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