p21-Activated Kinase 1 Promotes Breast Tumorigenesis via Phosphorylation and Activation of the Calcium/Calmodulin-Dependent Protein Kinase II

• DOI: 10.3389/fcell.2021.759259
• Publication Date: 2022-01-17T11:52:36Z
• Authors: Héctor I. Saldiva...; Olga Villamar-Cruz; Claire M. Wells; Ibrahim Oguz; Federica Spaggiari; Jonathan Chernoff; Genaro Patiño-López; Sara Huerta-Yepez; Mayra Montecillo-...; Clara M. Rivera-P...; Marco A. Loza-Mejía; Alonso Vivar-Sierra; Paola Briseño-Díaz; Alejandro Zentell...; Alfonso Leon-Del-Rio; Alejandro López-S...; Laura Padierna-Mota; María de Jesús Ib...; José Esparza-López; Rosaura Hernández...; Luis E. Arias-Romero
• Keywords: PAK1

p21-Activated kinase-1 (Pak1) is frequently overexpressed and/or amplified in human breast cancer and necessary for transformation of mammary epithelial cells. Here, we show that Pak1 interacts with phosphorylates the Calcium/Calmodulin-dependent Protein Kinase II (CaMKII), pharmacological inhibition or depletion leads to diminished activity CaMKII. We found a strong correlation between CaMKII expression samples, combined small-molecule inhibitors was synergistic induced apoptosis more potently Her2 positive triple negative (TNBC) Co-adminstration Pak resulted dramatic reduction proliferation an increase 3D cell culture setting, as well impairment migration invasion TNBC Finally, mice bearing xenografts cells showed significant delay tumor growth when treated These data delineate signaling pathway from required efficient proliferation, cells, suggest new therapeutic strategies cancer.