N-terminal truncation of Lats1 causes abnormal cell growth control and chromosomal instability

Yabuta, Norikazu; Mukai, Satomi; Okamoto, Ayumi; Okuzaki, Daisuke; Suzuki, Hirokazu; Torigata, Kosuke; Yoshida, Kaori; Okada, Nobuhiro; Miura, Daisaku; Ito, Akihiko; Ikawa, Masahito; Okabe, Masaru; Nojima, Hiroshi

doi:https://doi.org/10.1242/jcs.113431

N-terminal truncation of Lats1 causes abnormal cell growth control and chromosomal instability

Yabuta, Norikazu; Mukai, Satomi; Okamoto, Ayumi et al.

Journal of Cell Science, 2013, 126(2), 508-519

アクセス数:312件（2025-04-18 02:06 集計）

固定URL: https://hdl.handle.net/11094/78607

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タイトル	N-terminal truncation of Lats1 causes abnormal cell growth control and chromosomal instability
著者	NRID 1000010343245 1000010343245 researchmap permalink read0092303 read0092303 Scopus Author ID 6603956412 6603956412 著者名 Yabuta, Norikazu
	NRID 1000010706146 1000010706146 著者名 Mukai, Satomi
	著者名 Okamoto, Ayumi
	NRID 1000000346131 1000000346131 ORCID 0000-0002-4552-783X 0000-0002-4552-783X researchmap permalink read0092307 read0092307 Scopus Author ID 6506703054 6506703054 著者名 Okuzaki, Daisuke
	著者名 Suzuki, Hirokazu
	著者名 Torigata, Kosuke
	著者名 Yoshida, Kaori
	著者名 Okada, Nobuhiro
	NRID 1000060510873 1000060510873 著者名 Miura, Daisaku
	NRID 1000080273647 1000080273647 著者名 Ito, Akihiko
	NRID 1000020304066 1000020304066 ORCID 0000-0001-9859-6217 0000-0001-9859-6217 researchmap permalink read0054910 read0054910 Scopus Author ID 16689054500 16689054500 著者名 Ikawa, Masahito
	NRID 1000030089875 1000030089875 著者名 Okabe, Masaru
	著者名 Nojima, Hiroshi
キーワード等	Chromosome instability
	Hippo
	Lats1
	Lats2
	YAP
抄録	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 (Lats1δN/δN). Some Lats1δN/δN mice were born safely and grew normally. However, mouse embryonic fibroblasts (MEFs) from Lats1δN/δN 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. Lats1δN/δN 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 Lats1δN/δN 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.
出版者	Company of Biologists Ltd
収録物名	Journal of Cell Science
巻(号)	126(2)
ページ	508-519
刊行年月	2013-01-15
言語	英語
ハンドルURL	https://hdl.handle.net/11094/78607
PISSN	00219533
eISSN	14779137
NCID	AA00694823
関連情報 (isIdenticalTo)	DOI (出版社版) https://doi.org/10.1242/jcs.113431
関連情報 (isIdenticalTo)	PMID 23230145
アクセス権	open access
権利情報	© 2013. Published by The Company of Biologists Ltd.
出版タイプ	Version of Record
カテゴリ	学術雑誌論文 Journal Article

資源タイプ	学術雑誌論文
ローカル資源タイプ	学術雑誌論文
DCTERMS.bibliographicCitation	Journal of Cell Science. 2013, 126(2), p. 508-519
DC.title	N-terminal truncation of Lats1 causes abnormal cell growth control and chromosomal instability
DC.creator	Yabuta, Norikazu
	Mukai, Satomi
	Okamoto, Ayumi
	Okuzaki, Daisuke
	Suzuki, Hirokazu
	Torigata, Kosuke
	Yoshida, Kaori
	Okada, Nobuhiro
	Miura, Daisaku
	Ito, Akihiko
	Ikawa, Masahito
	Okabe, Masaru
	Nojima, Hiroshi
DC.publisher	Company of Biologists Ltd
DC.language' scheme='DCTERMS.RFC1766	英語
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2013-01-15
DC.identifier	https://doi.org/10.1242/jcs.113431
DC.subject	Chromosome instability
	Hippo
	Lats1
	Lats2
	YAP
DCTERMS.abstract	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 (Lats1δN/δN). Some Lats1δN/δN mice were born safely and grew normally. However, mouse embryonic fibroblasts (MEFs) from Lats1δN/δN 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. Lats1δN/δN 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 Lats1δN/δN 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.
DC.rights	© 2013. Published by The Company of Biologists Ltd.
DC.format	78607
citation_title	N-terminal truncation of Lats1 causes abnormal cell growth control and chromosomal instability
citation_author	Yabuta, Norikazu
	Mukai, Satomi
	Okamoto, Ayumi
	Okuzaki, Daisuke
	Suzuki, Hirokazu
	Torigata, Kosuke
	Yoshida, Kaori
	Okada, Nobuhiro
	Miura, Daisaku
	Ito, Akihiko
	Ikawa, Masahito
	Okabe, Masaru
	Nojima, Hiroshi
citation_publisher	Company of Biologists Ltd
citation_language	英語
citation_date	2013-01-15
citation_journal_title	Journal of Cell Science
citation_volume	126
citation_issue	2
citation_firstpage	508
citation_lastpage	519
citation_doi	https://doi.org/10.1242/jcs.113431
citation_pmid	23230145
citation_public_url	https://hdl.handle.net/11094/78607

N-terminal truncation of Lats1 causes abnormal cell growth control and chromosomal instability

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