In:
The FASEB Journal, Wiley, Vol. 33, No. 12 ( 2019-12), p. 13683-13694
Abstract:
Gα 13 , a heterotrimeric G‐protein of the Gα 12/13 subfamily, is associated with aggressive phenotypes in various human cancers. However, the mechanisms by which Gα 13 promotes cancer progression have not been fully elucidated. Here, we demonstrate that the activation of Ga13 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 Gα 13 ‐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 Gα 13 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. Gα 13 ‐mediated LATS1 down‐regulation contributes to epithelial‐mesenchymal transition in ovarian cancer. FASEB J. 33, 13683‐13694 (2019). www.fasebj.org
Type of Medium:
Online Resource
ISSN:
0892-6638
,
1530-6860
DOI:
10.1096/fj.201901278R
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
1468876-1
detail.hit.zdb_id:
639186-2
SSG:
12
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