| First Author | Yabuta N | Year | 2013 |
| Journal | J Cell Sci | Volume | 126 |
| Issue | Pt 2 | Pages | 508-20 |
| PubMed ID | 23230145 | Mgi Jnum | J:200232 |
| Mgi Id | MGI:5507912 | Doi | 10.1242/jcs.113431 |
| Citation | Yabuta N, et al. (2013) N-terminal truncation of Lats1 causes abnormal cell growth control and chromosomal instability. J Cell Sci 126(Pt 2):508-20 |
| abstractText | The tumor suppressors Lats1 and Lats2 are mediators of the Hippo pathway that regulates tissue growth and proliferation. Their N-terminal non-kinase regions are distinct except for Lats conserved domains 1 and 2 (LCD1 and LCD2), which may be important for Lats1/2-specific functions. Lats1 knockout mice were generated by disrupting the N-terminal region containing LCD1 (Lats1(DeltaN/DeltaN)). Some Lats1(DeltaN/DeltaN) mice were born safely and grew normally. However, mouse embryonic fibroblasts (MEFs) from Lats1(DeltaN/DeltaN) mice displayed mitotic defects, centrosomal overduplication, chromosomal misalignment, multipolar spindle formation, chromosomal bridging and cytokinesis failure. They also showed anchorage-independent growth and continued cell cycles and cell growth, bypassing cell-cell contact inhibition similar to tumor cells. Lats1(DeltaN/DeltaN) MEFs produced tumors in nude mice after subcutaneous injection, although the tumor growth rate was much slower than that of ordinary cancer cells. Yap, a key transcriptional coactivator of the Hippo pathway, was overexpressed and stably retained in Lats1(DeltaN/DeltaN) MEFs in a cell density independent manner, and Lats2 mRNA expression was downregulated. In conclusion, N-terminally truncated Lats1 induced Lats2 downregulation and Yap protein accumulation, leading to chromosomal instability and tumorigenesis. |
