title: N-α-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity.
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.
authors.affiliation: Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei 100, Taiwan.
authors.forename: Kuo-Tai
authors.initials: KT
authors.lastname: Hua
authors.forename: Ching-Ting
authors.initials: CT
authors.lastname: Tan
authors.forename: Gunnar
authors.initials: G
authors.lastname: Johansson
authors.forename: Jang-Ming
authors.initials: JM
authors.lastname: Lee
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Yang
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Lu
authors.forename: Chi-Kuan
authors.initials: CK
authors.lastname: Chen
authors.forename: Jen-Liang
authors.initials: JL
authors.lastname: Su
authors.forename: Poshen B
authors.initials: PB
authors.lastname: Chen
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Wu
authors.forename: Chia-Chun
authors.initials: CC
authors.lastname: Chi
authors.forename: Hsin-Jung
authors.initials: HJ
authors.lastname: Kao
authors.forename: Hou-Jung
authors.initials: HJ
authors.lastname: Shih
authors.forename: Min-Wei
authors.initials: MW
authors.lastname: Chen
authors.forename: Ming-Hsien
authors.initials: MH
authors.lastname: Chien
authors.forename: Pai-Sheng
authors.initials: PS
authors.lastname: Chen
authors.forename: Wei-Jiunn
authors.initials: WJ
authors.lastname: Lee
authors.forename: Tsu-Yao
authors.initials: TY
authors.lastname: Cheng
authors.forename: George
authors.initials: G
authors.lastname: Rosenberger
authors.forename: Chee-Yin
authors.initials: CY
authors.lastname: Chai
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Yang
authors.forename: Ming-Shyan
authors.initials: MS
authors.lastname: Huang
authors.forename: Tsung-Ching
authors.initials: TC
authors.lastname: Lai
authors.forename: Teh-Ying
authors.initials: TY
authors.lastname: Chou
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism / Q000502:physiology*; D000368:Aged; D002465:Cell Movement; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D063209:N-Terminal Acetyltransferase A; D063213:N-Terminal Acetyltransferase E; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D064067:Rho Guanine Nucleotide Exchange Factors; D020764:cdc42 GTP-Binding Protein / Q000037:antagonists & inhibitors*; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors*
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D064067:Rho Guanine Nucleotide Exchange Factors; D000123:Acetyltransferases; D063209:N-Terminal Acetyltransferase A; C504824:NAA10 protein, human; D063213:N-Terminal Acetyltransferase E; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein