8260

NAA10

N(alpha)-acetyltransferase 10, NatA catalytic subunit;NAA10;N(alpha)-acetyltransferase 10, NatA catalytic subunit

ARD1 homolog A, N-acetyltransferase|N-acetyltransferase ARD1, human homolog of|N-alpha-acetyltransferase 10|N-alpha-acetyltransferase 10, NatA catalytic subunit|N-terminal acetyltransferase complex ARD1 subunit homolog A|natA catalytic subunit Naa10

Xq28

protein-coding

INTRODUCTION: Combination of multiple biomarkers representing distinct aspects of tumor biology will have a better prognostic value. This study was to identify prognostic subgroups of colon adenocarcinoma by combined analysis of synuclein-gamma (SNCG), a human homologue of piwi (Hiwi), phosphatase of regenerating liver-3 (PRL-3), arrest-defective protein 1, homolog A (ARD1) and clinicopathologic features in 225 colon adenocarcinoma specimens. METHODS: Immunohistochemistry for 4 tumor markers was performed in whole tissue sections from 225 colon adenocarcinoma patients with complete clinicopathologic data and up to 10-year follow-up. The immunohistochemical expression patterns were examined individually and in multimarker combinations. Univariate and multivariate analyses were performed to identify independent predictive markers of poor outcome. RESULTS: With the tumor marker positive rate [32.0% (62/225) for SNCG; 76.9% (173/225) for combined SNCG/Hiwi/PRL-3/ARD1] and the detecting accuracy [61.9% (252/407) for SNCG; 82.6% (336/407) for combined SNCG/Hiwi/PRL-3/ARD1] increasing, incremental value of combined SNCG/Hiwi/PRL-3/ARD1 (P < 0.001; hazard ratios (HR), 3.2) to poor outcome was found. Stratified by lymph node, Hiwi alone (P = 0.004; HR, 3.2) led to poor outcome in patients without lymph node metastasis (LN-), and SNCG (P < 0.001; HR, 2.5) had independently poor prognostic value for patients with lymph node metastasis (LN+). CONCLUSIONS: Multimarker phenotypes improved tumor positive rate, detecting accuracy and prognostic value. In addition, a subgroup of more aggressive tumors can be identified by evaluating Hiwi level in LN- cancer, and SNCG level in LN+ cancer.

N-alpha-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.