13-mediated LATS1 down-regulation contributes to epithelial-mesenchymal transition in ovarian cancer

Hiroshi Yagi, Ichiro Onoyama, Kazuo Asanoma, Emiko Hori, Masafumi Yasunaga, Keisuke Kodama, Masako Kijima, Tatsuhiro Ohgami, Eisuke Kaneki, Kaoru Okugawa, Hideaki Yahata, Kiyoko Kato

Research output: Contribution to journalArticle

Abstract

Gα13, a heterotrimeric G-protein of the Gα12/13 subfamily, is associated with aggressive phenotypes in various human cancers. However, the mechanisms by which Gα13 promotes cancer progression have not been fully elucidated. Here, we demonstrate that the activation of Gα13 induces epithelial-mesenchymal transition in ovarian cancer (OvCa) cells through down-regulation of large tumor suppressor kinase (LATS) 1, a critical component of the Hippo signaling pathway. A synthetic biology approach using a mutant GPCR and chimeric G-protein revealed that Gα13-regulated phosphorylation of LATS1 at serine 909 within its activation loop induced recruitment of the itchy E3 ubiquitin protein ligase to trigger LATS1 degradation. Our findings uncover novel mechanisms through which Gα13 activation induces dysregulation of the Hippo signaling pathway, which leads to aggressive cancer phenotypes, and thereby identify a potential target for preventing the metastatic spread of OvCa.-Yagi, H., Onoyama, I., Asanoma, K., Hori, E., Yasunaga, M., Kodama, K., Kijima, M., Ohgami, T., Kaneki, E., Okugawa, K., Yahata, H., Kato, K. Gα13-mediated LATS1 down-regulation contributes to epithelial-mesenchymal transition in ovarian cancer.

Original languageEnglish
Pages (from-to)13683-13694
Number of pages12
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume33
Issue number12
DOIs
Publication statusPublished - Dec 1 2019

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Epithelial-Mesenchymal Transition
Ovarian Neoplasms
Down-Regulation
Chemical activation
G12-G13 GTP-Binding Protein alpha Subunits
Heterotrimeric GTP-Binding Proteins
Neoplasms
Phosphorylation
Ubiquitin-Protein Ligases
Synthetic Biology
Phenotype
GTP-Binding Proteins
Serine
Tumors
Phosphotransferases
Cells
Degradation

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

13-mediated LATS1 down-regulation contributes to epithelial-mesenchymal transition in ovarian cancer. / Yagi, Hiroshi; Onoyama, Ichiro; Asanoma, Kazuo; Hori, Emiko; Yasunaga, Masafumi; Kodama, Keisuke; Kijima, Masako; Ohgami, Tatsuhiro; Kaneki, Eisuke; Okugawa, Kaoru; Yahata, Hideaki; Kato, Kiyoko.

In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology, Vol. 33, No. 12, 01.12.2019, p. 13683-13694.

Research output: Contribution to journalArticle

Yagi, Hiroshi ; Onoyama, Ichiro ; Asanoma, Kazuo ; Hori, Emiko ; Yasunaga, Masafumi ; Kodama, Keisuke ; Kijima, Masako ; Ohgami, Tatsuhiro ; Kaneki, Eisuke ; Okugawa, Kaoru ; Yahata, Hideaki ; Kato, Kiyoko. / 13-mediated LATS1 down-regulation contributes to epithelial-mesenchymal transition in ovarian cancer. In: FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2019 ; Vol. 33, No. 12. pp. 13683-13694.
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