N-α-Acetyltransferase 10 Protein Suppresses Cancer Cell Metastasis by Binding PIX Proteins and Inhibiting Cdc42/Rac1 Activity

Kuo Tai Hua; Ching Ting Tan; Gunnar Johansson; Jang Ming Lee; Pei Wen Yang; Hsin Yi Lu; Chi Kuan Chen; Jen Liang Su; PoShen B. Chen; Yu Ling Wu; Chia Chun Chi; Hsin Jung Kao; Hou Jung Shih; Min Wei Chen; Ming Hsien Chien; Pai Sheng Chen; Wei Jiunn Lee; Tsu Yao Cheng; George Rosenberger; Chee Yin Chai; Chih Jen Yang; Ming Shyan Huang; Tsung Ching Lai; Teh Ying Chou; Michael Hsiao; Min Liang Kuo

doi:10.1016/j.ccr.2010.11.010

N-α-Acetyltransferase 10 Protein Suppresses Cancer Cell Metastasis by Binding PIX Proteins and Inhibiting Cdc42/Rac1 Activity

Kuo Tai Hua, Ching Ting Tan, Gunnar Johansson, Jang Ming Lee, Pei Wen Yang, Hsin Yi Lu, Chi Kuan Chen, Jen Liang Su, PoShen B. Chen, Yu Ling Wu, Chia Chun Chi, Hsin Jung Kao, Hou Jung Shih, Min Wei Chen, Ming Hsien Chien, Pai Sheng Chen, Wei Jiunn Lee, Tsu Yao Cheng, George Rosenberger, Chee Yin ChaiChih Jen Yang, Ming Shyan Huang, Tsung Ching Lai, Teh Ying Chou, Michael Hsiao, Min Liang Kuo

Research output: Contribution to journal › Article › peer-review

89 Citations (Scopus)

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.

Original language	English
Pages (from-to)	218-231
Number of pages	14
Journal	Cancer Cell
Volume	19
Issue number	2
DOIs	https://doi.org/10.1016/j.ccr.2010.11.010
Publication status	Published - Feb 15 2011
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccr.2010.11.010

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Hua, K. T., Tan, C. T., Johansson, G., Lee, J. M., 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., Cheng, T. Y., Rosenberger, G., ... Kuo, M. L. (2011). N-α-Acetyltransferase 10 Protein Suppresses Cancer Cell Metastasis by Binding PIX Proteins and Inhibiting Cdc42/Rac1 Activity. Cancer Cell, 19(2), 218-231. https://doi.org/10.1016/j.ccr.2010.11.010

Hua, KT, Tan, CT, Johansson, G, Lee, JM, Yang, PW, Lu, HY, Chen, CK, Su, JL, Chen, PB, Wu, YL, Chi, CC, Kao, HJ, Shih, HJ, Chen, MW, Chien, MH, Chen, PS, Lee, WJ, Cheng, TY, Rosenberger, G, Chai, CY, Yang, CJ, Huang, MS, Lai, TC, Chou, TY, Hsiao, M & Kuo, ML 2011, 'N-α-Acetyltransferase 10 Protein Suppresses Cancer Cell Metastasis by Binding PIX Proteins and Inhibiting Cdc42/Rac1 Activity', Cancer Cell, vol. 19, no. 2, pp. 218-231. https://doi.org/10.1016/j.ccr.2010.11.010

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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.",

author = "Hua, {Kuo Tai} and Tan, {Ching Ting} and Gunnar Johansson and Lee, {Jang Ming} and Yang, {Pei Wen} and Lu, {Hsin Yi} and Chen, {Chi Kuan} and Su, {Jen Liang} and Chen, {PoShen B.} and Wu, {Yu Ling} and Chi, {Chia Chun} and Kao, {Hsin Jung} and Shih, {Hou Jung} and Chen, {Min Wei} and Chien, {Ming Hsien} and Chen, {Pai Sheng} and Lee, {Wei Jiunn} and Cheng, {Tsu Yao} and George Rosenberger and Chai, {Chee Yin} and Yang, {Chih Jen} and Huang, {Ming Shyan} and Lai, {Tsung Ching} and Chou, {Teh Ying} and Michael Hsiao and Kuo, {Min Liang}",

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AU - Hua, Kuo Tai

AU - Tan, Ching Ting

AU - Johansson, Gunnar

AU - Lee, Jang Ming

AU - Yang, Pei Wen

AU - Lu, Hsin Yi

AU - Chen, Chi Kuan

AU - Su, Jen Liang

AU - Chen, PoShen B.

AU - Wu, Yu Ling

AU - Chi, Chia Chun

AU - Kao, Hsin Jung

AU - Shih, Hou Jung

AU - Chen, Min Wei

AU - Chien, Ming Hsien

AU - Chen, Pai Sheng

AU - Lee, Wei Jiunn

AU - Cheng, Tsu Yao

AU - Rosenberger, George

AU - Chai, Chee Yin

AU - Yang, Chih Jen

AU - Huang, Ming Shyan

AU - Lai, Tsung Ching

AU - Chou, Teh Ying

AU - Hsiao, Michael

AU - Kuo, Min Liang

PY - 2011/2/15

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N2 - 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.

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N-α-Acetyltransferase 10 Protein Suppresses Cancer Cell Metastasis by Binding PIX Proteins and Inhibiting Cdc42/Rac1 Activity

Abstract

ASJC Scopus subject areas

UN SDGs

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