N-α-Acetyltransferase 10 Protein Suppresses Cancer Cell Metastasis by Binding PIX Proteins and Inhibiting Cdc42/Rac1 Activity
Journal
Cancer Cell
Journal Volume
19
Journal Issue
2
Pages
218-231
Date Issued
2011
Author(s)
Johansson G.
Yang P.-W.
Lu H.-Y.
Chen C.-K.
Su J.-L.
Chen P.B.
Wu Y.-L.
Chi C.-C.
Kao H.-J.
Shih H.-J.
Chen M.-W.
Chien M.-H.
Chen P.-S.
Lee W.-J.
Rosenberger G.
Chai C.-Y.
Yang C.-J.
Huang M.-S.
Lai T.-C.
Chou T.-Y.
Hsiao M.
Kuo M.-L.
Abstract
N-α-acetyltransferase 10 protein, Naa10p, is an N-acetyltransferase known to be involved in cell cycle control. We found that Naa10p was expressed lower in varieties of malignancies with lymph node metastasis compared with non-lymph node metastasis. Higher Naa10p expression correlates the survival of lung cancer patients. Naa10p significantly suppressed migration, tumor growth, and metastasis independent of its enzymatic activity. Instead, Naa10p binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activity and decreased cell migration. Forced expression of PIX in Naa10-transfected tumor cells restored the migration and metastasis ability. We suggest that Naa10p functions as a tumor metastasis suppressor by disrupting the migratory complex, PIX-GIT- Paxillin, in cancer cells. ? 2011 Elsevier Inc.
SDGs
Other Subjects
acyltransferase; binding protein; n alpha acetyltransferase 10; p21 activated kinase interacting exchange factor; paxillin; protein Cdc42; Rac1 protein; unclassified drug; adult; animal experiment; animal model; animal tissue; article; cancer cell; cancer survival; cell migration; cell motility; complex formation; controlled study; enzyme activity; female; genetic transfection; human; human cell; human tissue; lung cancer; lymph node metastasis; major clinical study; male; metastasis inhibition; metastasis potential; mouse; nonhuman; priority journal; protein binding; protein domain; protein expression; protein protein interaction
Type
journal article