title: Geranylgeranylation signals to the Hippo pathway for breast cancer cell proliferation and migration.
abstract: 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.
authors.affiliation: Weis Center for Research, Danville, PA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Mi
authors.affiliation: 1] Weis Center for Research, Danville, PA, USA [2] School of Medical Sciences and Laboratory Medicine, Jiangsu University, Zhenjiang, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Weis Center for Research, Danville, PA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Childress
authors.affiliation: 1] Weis Center for Research, Danville, PA, USA [2] Department of Medicine, Mount Sinai Medical School, New York, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sudol
authors.affiliation: Weis Center for Research, Danville, PA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Robishaw
authors.affiliation: Weis Center for Research, Danville, PA, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: Berlot
authors.affiliation: Department of General Surgery, Geisinger Clinic, Danville, PA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Shabahang
authors.affiliation: Weis Center for Research, Danville, PA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Yang
mesh_terms: D000069059:Atorvastatin; D001549:Benzamides / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D057809:HEK293 Cells; D006538:Heptanoic Acids / Q000494:pharmacology; D000090683:Hippo Signaling Pathway; D006801:Humans; D061986:MCF-7 Cells; D054876:Prenylation / Q000502:physiology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D001549:Benzamides; C102521:GGTI 298; D006538:Heptanoic Acids; D011758:Pyrroles; D000069059:Atorvastatin; D017346:Protein Serine-Threonine Kinases
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