Geranylgeranylation signals to the Hippo pathway for breast cancer cell proliferation and migration.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5594 (Electronic) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE

Publication: <2002->: Basingstoke : Nature Publishing Group
Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987-

Cell Movement*/drug effects ; Cell Proliferation*/drug effects; Breast Neoplasms/*pathology ; Prenylation/*physiology ; Protein Serine-Threonine Kinases/*metabolism; Atorvastatin ; Benzamides/pharmacology ; Breast Neoplasms/metabolism ; Female ; HEK293 Cells ; Heptanoic Acids/pharmacology ; Hippo Signaling Pathway ; Humans ; MCF-7 Cells ; Protein Processing, Post-Translational/drug effects ; Pyrroles/pharmacology ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Tumor Cells, Cultured

Protein geranylgeranylation (GGylation) is an important biochemical process for many cellular signaling molecules. Previous studies have shown that GGylation is essential for cell survival in many types of cancer. However, the molecular mechanism mediating the cell survival effect remains elusive. In this report, we show that the Hippo pathway mediates GGylation-dependent cell proliferation and migration in breast cancer cells. Blockade of GGylation enhanced phosphorylation of Mst1/2 and Lats1, and inhibited YAP and TAZ activity and the Hippo-YAP/TAZ pathway-dependent transcription. The effect of GGylation blockade on inhibition of breast cancer cell proliferation and migration is dependent on the Hippo-YAP/TAZ signaling, in which YAP appears to regulate cell proliferation and TAZ to regulate cell migration. Furthermore, GGylation-dependent cell proliferation is correlated with the activity of YAP/TAZ in breast cancer cells. Finally, Gγ and RhoA are the GGylated proteins that may transduce GGylation signals to the Hippo-YAP/TAZ pathway. Taken together, our studies have demonstrated that the Hippo-YAP/TAZ pathway is essential for GGylation-dependent cancer cell proliferation and migration.

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R01GM050369 United States GM NIGMS NIH HHS

0 (Benzamides)
0 (GGTI 298)
0 (Heptanoic Acids)
0 (Pyrroles)
A0JWA85V8F (Atorvastatin)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)

Date Created: 20140812 Date Completed: 20150826 Latest Revision: 20220408

20240829

10.1038/onc.2014.251

25109332