Expression profiling in primary embryonic fibroblasts deficient for the N-terminal truncation of Lats1
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ABSTRACT: Lats1 and Lats2 are the mediators of the Hippo pathway that regulates tissue growth and proliferation. Lats1 and Lats2 kinases share 85% sequence identity in the kinase domain. However, their non-kinase regions at the N-terminus are distinct except for Lats conserved domain 1 (LCD1) and LCD2, suggesting that their N-terminal regions are important for Lats1/2-specific functions. In this study, we generated Lats1 knockout mice disrupting the N-terminal region containing LCD1 (Lats1ΔN/ΔN). We show that some Lats1ΔN/ΔN mice were born safely and grew normally. However, mouse embryonic fibroblasts (MEFs) from Lats1ΔN/ΔN mice displayed drastic defects in mitosis, showing enhanced centrosome overduplication, chromosomal misalignment, multipolar spindle formation, chromosome bridging, and cytokinesis failure. Moreover, they displayed accelerated cell cycle and cell growth bypassing a cell-cell contact inhibition like tumor cells, and exhibited anchorage independent growth. Indeed, Lats1ΔN/ΔN MEFs produced tumors in nude mice after subcutaneous injection, although the tumor growth rate was much slower than ordinary cancer cells. Furthermore, Yap, the key transcriptional co-activator in the Hippo pathway, was overexpressed and retained stable in Lats1ΔN/ΔN MEFs under high cell density, and expression of Lats2 mRNA were down-regulated.
ORGANISM(S): Mus musculus
PROVIDER: GSE37871 | GEO | 2012/12/17
SECONDARY ACCESSION(S): PRJNA164681
REPOSITORIES: GEO
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