YWHAZ, also named 14-3-3ζ, is a central hub protein involved in many signal transduction pathways. It plays a significant role in controlling cellular proliferation, migration, and differentiation. YWHAZ is associated with pathways like PI3K-Akt-mTOR, and influences vital cellular processes such as metabolism, apoptosis, and cell cycle regulation [1,2,3].

In cancer research, YWHAZ is frequently up-regulated in multiple cancer types. In gastric cancer, TMEM65 promotes tumorigenesis by targeting YWHAZ to activate the PI3K-Akt-mTOR pathway [2]. In ovarian cancer, YWHAZ promotes metastasis by modulating glycolysis, and its silencing inhibits cell proliferation, migration, and in vivo metastasis [3]. In breast cancer, YWHAZ interacts with DAAM1 to promote cell migration [4]. In bladder cancer, YWHAZ amplification/overexpression defines aggressive cancer and contributes to chemo -/radio-resistance by suppressing caspase-mediated apoptosis [5]. In gastric cancer, knockdown of YWHAZ inhibits cell migration, invasion, and EMT, and restrains the activation of the wnt/β-catenin signalling pathway [6]. In non-small cell lung cancer, miR-3074-5p suppresses cancer progression by targeting the YWHAZ/Hsp27 axis [7]. In hepatocellular carcinoma, wogonin inhibits cell proliferation by targeting the miR-27b-5p/YWHAZ axis [8].

In conclusion, YWHAZ plays crucial roles in various biological processes, especially in cancer progression. Studies on YWHAZ in different cancer models help to understand its functions in promoting tumorigenesis, metastasis, and resistance to treatment, providing potential therapeutic targets for cancer treatment.