Large tumor suppressor kinase 1 (LATS1) (LATS1)

Large tumor suppressor kinase 1 (LATS1) is a critical serine/threonine kinase and a central component of the Hippo signaling pathway, which regulates organ size and tissue homeostasis (UniProt, PMC) [2, 9]. By phosphorylating the oncoproteins YAP and TAZ, LATS1 promotes their cytoplasmic retention and degradation, thereby acting as a potent tumor suppressor that limits cell proliferation and induces apoptosis (UniProt, NIH) [2, 7]. In many cancers, such as breast and colorectal cancer, LATS1 expression or activity is frequently lost through genetic deletion or promoter hypermethylation, leading to uncontrolled growth and metastasis (PMC) [4, 10]. Conversely, pharmacological inhibition of LATS1 is being investigated as a therapeutic strategy in regenerative medicine to temporarily activate YAP/TAZ and promote tissue repair in the liver, heart, and skin (PMC, PubMed) [9, 12]. However, therapeutic targeting of LATS1 requires careful balancing, as sustained inhibition poses a risk of promoting tumorigenesis, while its activation in cancer remains a challenging pharmacological goal (PMC) [9, 11]. Emerging research also highlights LATS1's role in modulating tumor immunogenicity and the actin cytoskeleton (PMC) [10, 11].

Other names

WARTS protein kinaseh-wartsLarge tumor suppressor homolog 1Serine/threonine-protein kinase LATS1

Large tumor suppressor kinase 1 (LATS1) acts as the core catalytic component of the Hippo signaling pathway. It is activated by upstream kinases (MST1/2) and subsequently phosphorylates the transcriptional co-activators Yes-associated protein 1 (YAP1) and WW-domain-containing transcription regulator protein 1 (TAZ/WWTR1). This phosphorylation promotes their cytoplasmic sequestration via 14-3-3 binding and targets them for proteasomal degradation, thereby inhibiting the expression of genes involved in cell survival and proliferation. Inhibitors of LATS1 are designed to release this brake, allowing YAP/TAZ nuclear translocation to drive regenerative processes (UniProt, PMC) [2, 9, 12].