Focal adhesion kinase (FAK)-Protein kinase B (Akt)-Ribosomal protein S6 kinase beta-1 (p70S6K) signaling pathway (FAK-Akt-p70S6K)

The Focal adhesion kinase (FAK)-Protein kinase B (Akt)-Ribosomal protein S6 kinase beta-1 (p70S6K) signaling pathway is a critical intracellular cascade that integrates signals from the extracellular matrix and growth factors to regulate fundamental cellular processes [1, 7]. Focal Adhesion Kinase (FAK) acts as a scaffold and kinase at focal adhesions, activating the Phosphoinositide 3-kinase (PI3K)/Akt axis, which subsequently triggers p70 ribosomal S6 kinase (p70S6K) to promote protein synthesis and cell cycle progression [5, 8, 11]. This pathway is frequently hyperactivated in various malignancies, where it drives tumor cell survival, migration, invasion, and resistance to therapy [1, 2, 4]. Therapeutic strategies often involve small molecule inhibitors targeting individual nodes like FAK or Akt, or combination therapies to prevent compensatory feedback mechanisms [2, 10, 15]. Dysregulation of this axis is also implicated in fibrotic diseases and metabolic disorders, making it a focal point for multi-target drug development [14]. In addition to its role in oncology, the pathway is involved in regulating autophagy and the actin cytoskeleton, further influencing cell motility and environmental adaptation [1, 11]. Monitoring biomarkers such as the phosphorylation status of FAK, Akt, and p70S6K is essential for assessing pathway activity and therapeutic response in clinical settings [1, 9].

Other names

FAK/Akt/p70S6K axisFAK-PI3K-Akt-p70S6K pathwayFAK-Akt-mTOR-p70S6K pathwayPTK2-AKT-RPS6KB1 signaling

Inhibition of phosphorylation at key regulatory sites (e.g., FAK Y397, Akt S473, p70S6K T389) to disrupt downstream signaling for cell growth, survival, and migration.