Yes1-flox Mouse

YES1, a nonreceptor tyrosine kinase, belongs to the SRC family of kinases (SFK) and controls multiple cancer signaling pathways. It plays a key role in cancer cell proliferation, adhesion, invasion, survival, and angiogenesis during tumorigenesis and tumor development [1,2]. YES1 is involved in pathways like EphA2-YES1-ANXA2 in gastric cancer [3], and its activation can phosphorylate downstream proteins.

Genetic depletion of YES1 in in vitro and in vivo models, such as in small cell lung cancer (SCLC) cell-and patient-derived xenografts, dramatically reduced cell proliferation, organoid formation, tumor growth, and distant metastasis, leading to extensive apoptosis and tumor regressions [4]. In triple-negative breast cancer (TNBC) models, disrupting YES1, either genetically or pharmacologically, induced aberrant mitosis, centrosome amplification, and chromosomal instability, and also potentiated the efficacy of taxanes [5]. In EGFR-TKI-resistant non-small cell lung cancer (NSCLC) cells, knockdown of YES1 suppressed cell proliferation, migration, and tumorigenicity [6].

In conclusion, YES1 is a crucial regulator in cancer development. Studies using gene-knockout or knockdown models in various cancer types, like SCLC, TNBC, and NSCLC, have revealed its role in promoting tumor growth, metastasis, and drug resistance. Targeting YES1 shows promise as a therapeutic strategy against cancer.