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Human homologue of Drosophila lats, LATS1, negatively regulate growth by inducing G2/M arrest or apoptosis

Abstract

The lats gene encodes a family of proteins conserved from insects to humans. Drosophila carrying lats mutant cells or mice deficient for Lats1 develop tumors in various tissues. The mammalian LATS1 protein was previously shown to bind to CDC2, suggesting that LATS1 may modulate G2/M cell cycle progression by affecting CDC2 activity. In this study, we introduced human LATS1 into LATS−/− MEF cells by adenovirus-mediated gene transfer. Overexpression of LATS1 causes G2/M arrest through inhibition of CDC2 kinase activity. Furthermore, overexpression of LATS1 significantly suppressed the human tumor cell growth in vitro and tumorigenicity in vivo by inducing either cell cycle arrest in G2/M or apoptosis. These observations suggest that LATS1 is a potent growth suppressor and, like other tumor suppressors, it suppresses growth by inducing cell cycle arrest or apoptosis.

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Acknowledgements

We thank Y Hao and K Sepaneck for assistance, Dr A Pater for reading the manuscript, Dr A Pater and G Chernenko at Memorial University of Newfoudland, Canada, and Dr H Sun at Yale University for kindly providing human cancer cell lines, and R Carbone at the Yale Cancer Center Flow Cytometry Shared Resource for FACS measurement and data analysis. Xiaolong Yang is an Anna Fuller Fellow and a recipient of the Medical Research Council of Canada Fellowships.

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Correspondence to Tian Xu.

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Yang, X., Li, Dm., Chen, W. et al. Human homologue of Drosophila lats, LATS1, negatively regulate growth by inducing G2/M arrest or apoptosis. Oncogene 20, 6516–6523 (2001). https://doi.org/10.1038/sj.onc.1204817

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