Stip1, also known as Hop, is a eukaryote-specific co-chaperone. It plays a crucial role in protein homeostasis by facilitating substrate transfer from Hsp70 to Hsp90 as part of a ternary complex, thus regulating the molecular chaperone functions of Hsp70 and Hsp90 [1].

In cancer research, high Stip1 expression is associated with shorter overall survival, earlier lymph node metastasis, and more advanced clinical stage in various cancers. For example, in colorectal cancer, Stip1 knockdown suppresses cell proliferation, migration, and invasion by inhibiting the STAT3 pathway [2]. In lung adenocarcinoma, elevated Stip1 expression enhances the cancer cells' proliferative, adhesive, and migratory abilities through the JAK2/STAT3 signaling pathway and epithelial-mesenchymal transition (EMT) [4]. Intracellular targeting of Stip1 inhibits cancer cell line growth and promotes caspase 3-dependent apoptotic cell death [3]. In bladder cancer, stronger Stip1 nuclear staining is related to worse overall survival, and stronger cytoplasmic immunostaining correlates with shorter progression-free survival in chemotherapy-treated patients [5]. Bioinformatics analysis also shows that Stip1 is highly expressed in most tumors, and its expression is correlated with tumor mutational burden, microsatellite instability, immune cell infiltration, and immunomodulatory factors [6].

In conclusion, Stip1 is a key co-chaperone in protein homeostasis. In cancer, its high expression is closely associated with poor prognosis and cancer progression, making it a potential prognostic biomarker and therapeutic target. Research on Stip1 in cancer helps to understand the molecular mechanisms of cancer development and may provide new strategies for cancer treatment.