Functional analysis of LATS protein kinases, products of novel tumor-suppressor genes

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The LATS1 and LATS2 genes are mammalian homologs of the Drosophila LATS (large tumor suppressor) gene that encodes a serine/threonine kinase. Although LATS2 is expressed in various human cancer cell lines, we identified some kidney tumor cell lines that do not express LATS2. Both LATS1 and Bcl-2 are highly phosphorylated in LATS2-positive but not in LATS2-deficient, paclitaxel-treated cells.In addition, LATS2-deficient cells are less sensitive to paclitaxel-induced apoptosis. Ectopic expression of LATS2 in LATS2-deficient cells restores paclitaxel sensitivity , resulting in the phosphorylation of LATS1 and Bcl-2, and the induction of apoptosis. These observations indicate that LATS2 is involved in M-phase progression through the control of LATS1 and Bcl-2 phosphorylation, thereby regulating cellular entry into apoptosis and suggest that the status of LATS kinase genes in clinical tumors may define their sensitivity to paclitaxel-mediated chemotherapy.