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lats2

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Official Full Name
large tumor suppressor kinase 2
Background
This gene encodes a serine/threonine protein kinase belonging to the LATS tumor suppressor family. The protein localizes to centrosomes during interphase, and early and late metaphase. It interacts with the centrosomal proteins aurora-A and ajuba and is required for accumulation of gamma-tubulin and spindle formation at the onset of mitosis. It also interacts with a negative regulator of p53 and may function in a positive feedback loop with p53 that responds to cytoskeleton damage. Additionally, it can function as a co-repressor of androgen-responsive gene expression. [provided by RefSeq, Jul 2008]
Synonyms
LATS2; large tumor suppressor kinase 2; KPM; serine/threonine-protein kinase LATS2; warts-like kinase; serine/threonine kinase KPM; large tumor suppressor homolog 2; serine/threonine-protein kinase kpm; LATS, large tumor suppressor, homolog 2; kinase phosphorylated during mitosis protein; LATS (large tumor suppressor, Drosophila) homolog 2; si:ch211-173o4.2

Recent Progress

LATS2 is a key component of the Hippo signaling pathway. It was reported that LATS2 inhibits Wnt/β-catenin-mediated oncogenesis by disrupting the β-catenin/BCL9 interaction. Nocodazole, an antimicrotubule drug, potently induced LATS2 to suppress tumor growth in vivo by targeting β-catenin/BCL9. The results suggest that LATS2 is not only a key tumor suppressor in human cancer, but may also be an important target for anticancer therapy.

Fig. 1. Domain architecture of the LATS2. (Li et al, 2013)

Another research displayed that mammalian LATS orthologues exhibit distinct expression profiles according to germ cell layer origin. LATS2−/− embryos show overgrowth in restricted tissues of mesodermal lineage, displaying centrosome amplification and genomic instability. LATS2 localizes to centrosomes and overexpression of LATS2 suppresses centrosome over-duplication. These findings indicated an essential role of LATS2 in governing centrosome duplication, maintenance of mitotic fidelity and genomic stability.

LATS2 has also been proved to be involved in embryo development and epithelial-to-mesenchymal transitions (EMTs), and Snail1 is a central regulator of epithelial cell adhesion and movement in EMT. By screening human kinome RNAi, researchers have identified Lats2 kinase is a novel regulator that modulates Snail1 protein level, subcellular localization, and thus, activity. Lats2 interacts with Snail1 and directly phosphorylates Snail1 at residue T203. This occurs in the nucleus and retains Snail1 in the nucleus thereby enhancing its stability. Taken together, Lats2 positively influence cellular EMT and tumor cell invasion in a Snail1-dependent manner.

LATS2 is also closely related to ovarian cancer (OC). Previous studies have shown that the expression of miR-25 is increased in OC tissues and cell lines, and inhibition of miR-25 remarkably suppresses proliferation, migration and invasion of OC cells. LATS2 is confirmed to be a direct target of miR-25 in OC cells. Moreover, restoration of LATS2 significantly attenuated the oncogenic effects of miR-25. Taken together, these data suggest an oncogenic role of miR-25 in OC and a potentially novel diagnostic and therapeutic target for OC treatment.

References:

  1. Li, J., et al. "LATS2 suppresses oncogenic Wnt signaling by disrupting β-catenin/BCL9 interaction." Cell Reports 5.6(2013):1650-1663.
  2. Mcpherson, J. P., et al. "Lats2/Kpm is required for embryonic development, proliferation control and genomic integrity." Embo Journal 23.18(2014):3677-3688.
  3. Zhang, K., et al. "Lats2 kinase potentiates Snail1 activity by promoting nuclear retention upon phosphorylation." Embo Journal 31.1(2014):29-43.
  4. Hoa, Lily, et al. "The characterisation of LATS2 kinase regulation in Hippo-YAP signalling." Cellular Signalling 28.5(2016):488-497.
  5. Feng, S., et al. "MiR-25 promotes ovarian cancer proliferation and motility by targeting LATS2." Tumour Biol 35.12(2014):12339-12344.