Rack1-flox Mouse

Rack1, also known as Receptor for activated C kinase 1, is a highly conserved intracellular adaptor protein and a ribosomal binding protein [3,4,6]. It functions as a scaffolding protein, binding to multiple signaling molecules simultaneously, stabilizing and anchoring proteins, and regulating translation [3]. Rack1 is involved in various signaling cascades, including those related to hormonal signaling, stress responses, and growth and development processes in plants, as well as in pathways like NF-κB in cancer-related contexts [1,5].

In oral squamous cell carcinoma (OSCC), high Rack1 expression correlates with increased M2 macrophage infiltration, promotes M2-like macrophage polarization via the NF-κB pathway, and is associated with poor prognosis [1]. In ovarian cancer, loss of SMURF2 expression enhances Rack1 stability, promoting cancer progression, as SMURF2 is an E3 ligase of Rack1 [2]. In breast cancer, Rack1 facilitates cancer progression by competitively inhibiting the binding of β-catenin to PSMD2, enhancing β-catenin stability, and activating the canonical WNT signaling pathway [7].

In conclusion, Rack1 is a versatile protein with a wide-reaching impact on biological processes. Its dysregulation is associated with the progression of multiple cancers, including OSCC, ovarian cancer, and breast cancer. Studies on Rack1, especially through loss-of-function models in these cancer types, have provided insights into its role in tumorigenesis, potentially guiding the development of targeted therapies.