TY - JOUR
T1 - POTEE promotes breast cancer cell malignancy by inducing invadopodia formation through the activation of SUMOylated Rac1
AU - Martínez-López, Angélica
AU - García-Casas, Ana
AU - Infante, Guiomar
AU - González-Fernández, Mónica
AU - Salvador, Nélida
AU - Lorente, Mar
AU - Mendiburu-Eliçabe, Marina
AU - Gonzalez-Moreno, Santiago
AU - Villarejo-Campos, Pedro
AU - Velasco, Guillermo
AU - Malliri, Angeliki
AU - Castillo-Lluva, Sonia
N1 - © 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
PY - 2024/3/1
Y1 - 2024/3/1
N2 - 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.
AB - 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.
KW - Humans
KW - Female
KW - Signal Transduction
KW - Podosomes/metabolism
KW - Breast Neoplasms
KW - rac1 GTP-Binding Protein/metabolism
KW - Cell Movement
KW - Cell Line, Tumor
U2 - 10.1002/1878-0261.13568
DO - 10.1002/1878-0261.13568
M3 - Article
C2 - 38098337
SN - 1574-7891
VL - 18
SP - 620
EP - 640
JO - Molecular Oncology
JF - Molecular Oncology
IS - 3
ER -
