Pxn, also known as paxillin, is a key component of the mechanotransducing machinery. It plays important roles in processes like focal adhesion (FA) assembly, integrin signaling, and mechanotransduction [2,3]. It is involved in various pathways, such as the PXN/AKT signaling cascade [4], and is associated with autophagy-related pathways [5]. Pxn is crucial for cell-matrix connection and the regulation of cell contraction, migration, and proliferation [2,3,5].

In a diethylnitrosamine-induced DDX17HKO mouse model, DDX17 deficiency led to a significant reduction in lung metastasis. High DDX17 induced intron 3 retention of PXN-AS1, producing a transcript (PXN-AS1-IR3) that promoted HCC metastasis by inducing MYC transcription activation [1]. In ovarian cancer, high PXN expression was associated with poor prognosis, and PXN promoted ovarian cancer cell proliferation, migration, and invasion by suppressing the p110β/Vps34/Beclin1 pathway [5]. In breast cancer, ULK1/2-mediated phosphorylation of PXN at S32 and S119 weakened homotypic interactions and liquid-liquid phase separation of PXN, impairing FA assembly and suppressing breast cancer cell migration [2].

In conclusion, Pxn is essential for multiple cellular functions and is involved in the progression of various cancers, including HCC, ovarian cancer, and breast cancer. The use of mouse models, such as the DDX17HKO mouse model, has been crucial in revealing the role of Pxn-related factors in cancer metastasis and other disease-related biological processes.