Lats1-KO Mouse

Lats1, short for large tumor suppressor 1, is a key kinase in the Hippo signaling pathway. The Hippo pathway is evolutionarily conserved and crucial for regulating various biological processes such as cell growth, fate decision, organ size control, and regeneration [6]. Lats1, along with Lats2, phosphorylates and inhibits YAP and TAZ, two major effectors of the Hippo pathway, thus playing a significant role in tumor suppression [2].

In murine syngeneic tumor models, loss of Lats1/2 in tumor cells inhibits tumor growth, and this regression requires adaptive immune responses. Lats1/2-null tumor cells secrete nucleic-acid-rich extracellular vesicles, inducing a type I interferon response, which improves tumor immunogenicity [1]. In endometrial cancer, Lats1/2 loss promotes tumor immune evasion through down-regulating MHC-I expression, independent of the Hippo-YAP pathway. Lats1/2 directly interact with and phosphorylate STAT1 to enhance MHC-I transcriptional activation [3]. In breast cancer, knockout of METTL3 or YTHDF2, which regulate Lats1 mRNA through m6A methylation, increases Lats1 mRNA expression and suppresses tumorigenesis [4]. In ovarian cancer cells, deletion of S1PR1 increases Lats1/2 expression, promoting cell senescence, while silencing Lats1/2 suppresses senescence [5].

In conclusion, Lats1, as a core component of the Hippo pathway, plays a vital role in tumor-related biological processes. Gene knockout studies in mouse models have revealed its significance in tumor immunity, immune evasion, and cancer cell senescence, providing potential targets for cancer immunotherapy and chemotherapy.