Lats1-flox Mouse

Lats1, short for large tumor suppressor 1, is a key kinase in the Hippo signaling pathway. This pathway is evolutionarily conserved and regulates multiple biological processes such as cell growth, fate decision, organ size control, and regeneration. The Hippo pathway's core in mammals includes kinases MST1/2 and LATS1/2, along with downstream effectors YAP and TAZ, which control transcriptional programs related to cell proliferation, survival, and more [3].

In tumor-related studies, loss-of-function experiments have shown significant impacts. In murine syngeneic tumor models, deletion of LATS1/2 in tumor cells inhibits tumor growth, and this regression depends on adaptive immune responses. LATS1/2-null tumor cells secrete nucleic-acid-rich extracellular vesicles, inducing a type I interferon response, thus improving 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, a crucial transcription factor for MHC-I upregulation in response to interferon-γ signaling [2].

In conclusion, Lats1, as part of the Hippo pathway, plays a significant role in modulating tumor immunogenicity and immune evasion in cancer. The use of gene knockout (KO) and conditional knockout (CKO) mouse models has revealed its importance in tumor-immune interactions, providing potential targets for cancer immunotherapy and highlighting its essential functions in maintaining normal biological processes related to the immune response against tumors.