Journal Article

POTEE promotes breast cancer cell malignancy by inducing invadopodia formation through the activation of SUMOylated Rac1

Salvador, Nélida, Mendiburu‐Eliçabe, Marina, Villarejo‐Campos, Pedro, García‐Casas, Ana, Lorente, Mar, Gonzalez‐Moreno, Santiago, Malliri, Angeliki, Velasco, Guillermo, Castillo‐Lluva, Sonia, González‐Fernández, Mónica, Martínez‐López, Angélica, Infante, Guiomar

2024

Overview

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. SUMOylation of the small GTPase Rac1 is essential for tumor cell dissemination. POTEE is identified as a novel Rac1‐SUMO1 effector, promoting breast cancer malignancy through invadopodium formation. POTEE activates Rac1 by recruiting TRIO‐GEF, increasing tumor cell metastasis in vitro and in vivo. Colocalization of POTEE and Rac1 correlates with aggressive breast cancer subtypes, suggesting POTEE as a potential therapeutic target.

• Publisher: John Wiley & Sons, Inc,Wiley
• Subject: Ankyrins / Antigens / Apoptosis / Botulinum toxin / Breast cancer / Breast Neoplasms / Cell adhesion & migration / Cell cycle / Cell Line, Tumor / Cell migration / Cell Movement / Cell proliferation / Enzymes / Ethylenediaminetetraacetic acid / Female / Health aspects / Humans / invadopodium / Kinases / Localization / Malignancy / Mass spectrometry / Metastases / Metastasis / Motility / Ovaries / Podosomes - metabolism / POTEE / Prostate / Proteins / Rac1 / rac1 GTP-Binding Protein - metabolism / Rac1 protein / Scientific imaging / Signal Transduction / Stem cells / SUMO protein / SUMOylation / Therapeutic targets / TRIO‐GEF / Tumors