A novel anti-CCN1 monoclonal antibody suppresses Rac-dependent cytoskeletal reorganization and migratory activities in breast cancer cells

Shr Jeng Jim Leu; Jung Sung Sung; Meng Ling Huang; Mei Yu Chen; Tsai Wei Tsai

doi:10.1016/j.bbrc.2013.04.045

A novel anti-CCN1 monoclonal antibody suppresses Rac-dependent cytoskeletal reorganization and migratory activities in breast cancer cells

Shr Jeng Jim Leu^*, Jung Sung Sung, Meng Ling Huang, Mei Yu Chen, Tsai Wei Tsai

^*Corresponding author for this work

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

12 Scopus citations

Abstract

CCN1, a secreted matrix-associated molecule, is involved in multiple cellular processes. Accumulating evidence supports that CCN1 plays an important role in tumorigenesis and progression of breast cancer. In this study, we have developed a novel CCN1 function-blocking monoclonal antibody (mAb), designated YM1B. YM1B binds to human CCN1 with high specificity, recognizing the native CCN1 structure with undisturbed disulfide linkages. Our analyses have mapped the YM1B recognition region to domain IV of CCN1, likely in proximity to the DM site. In breast cancer cells, CCN1 can induce actin reorganization, formation of lamellipodia, and cell migration/invasion through the αV integrins/Rac1/ERK signaling axis; these CCN1-dependent activities can be effectively suppressed by YM1B. Our results also suggest that YM1B may exert its CCN1-blocking effect by perturbing the interaction of CCN1 with vitronectin and fibronectin, which are ligands of αV integrins and instrumental for integrin activation. This CCN1-specific mAb may open a new potential avenue for therapeutic intervention of breast cancer progression.

Original language	English
Pages (from-to)	885-891
Number of pages	7
Journal	Biochemical and Biophysical Research Communications
Volume	434
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2013.04.045
State	Published - 17 May 2013

Keywords

Breast cancer
CCN1
Cell migration
Monoclonal antibody
Rac

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

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10.1016/j.bbrc.2013.04.045

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title = "A novel anti-CCN1 monoclonal antibody suppresses Rac-dependent cytoskeletal reorganization and migratory activities in breast cancer cells",

abstract = "CCN1, a secreted matrix-associated molecule, is involved in multiple cellular processes. Accumulating evidence supports that CCN1 plays an important role in tumorigenesis and progression of breast cancer. In this study, we have developed a novel CCN1 function-blocking monoclonal antibody (mAb), designated YM1B. YM1B binds to human CCN1 with high specificity, recognizing the native CCN1 structure with undisturbed disulfide linkages. Our analyses have mapped the YM1B recognition region to domain IV of CCN1, likely in proximity to the DM site. In breast cancer cells, CCN1 can induce actin reorganization, formation of lamellipodia, and cell migration/invasion through the αV integrins/Rac1/ERK signaling axis; these CCN1-dependent activities can be effectively suppressed by YM1B. Our results also suggest that YM1B may exert its CCN1-blocking effect by perturbing the interaction of CCN1 with vitronectin and fibronectin, which are ligands of αV integrins and instrumental for integrin activation. This CCN1-specific mAb may open a new potential avenue for therapeutic intervention of breast cancer progression.",

keywords = "Breast cancer, CCN1, Cell migration, Monoclonal antibody, Rac",

author = "{Jim Leu}, {Shr Jeng} and Sung, {Jung Sung} and Huang, {Meng Ling} and Chen, {Mei Yu} and Tsai, {Tsai Wei}",

note = "Funding Information: This work was supported by grants from the National Scientific Council ( NSC-95-2320-B010-019 , NSC-98-2320-B010-004 ), Taipei City Hospital ( 99-001-62-029 , 10101-62-064 ), and the Ministry of Education, Aim for the Top University Plan, Taiwan, ROC ( 100AC-D107 ). ",

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T1 - A novel anti-CCN1 monoclonal antibody suppresses Rac-dependent cytoskeletal reorganization and migratory activities in breast cancer cells

AU - Jim Leu, Shr Jeng

AU - Sung, Jung Sung

AU - Huang, Meng Ling

AU - Chen, Mei Yu

AU - Tsai, Tsai Wei

N1 - Funding Information: This work was supported by grants from the National Scientific Council ( NSC-95-2320-B010-019 , NSC-98-2320-B010-004 ), Taipei City Hospital ( 99-001-62-029 , 10101-62-064 ), and the Ministry of Education, Aim for the Top University Plan, Taiwan, ROC ( 100AC-D107 ).

PY - 2013/5/17

Y1 - 2013/5/17

N2 - CCN1, a secreted matrix-associated molecule, is involved in multiple cellular processes. Accumulating evidence supports that CCN1 plays an important role in tumorigenesis and progression of breast cancer. In this study, we have developed a novel CCN1 function-blocking monoclonal antibody (mAb), designated YM1B. YM1B binds to human CCN1 with high specificity, recognizing the native CCN1 structure with undisturbed disulfide linkages. Our analyses have mapped the YM1B recognition region to domain IV of CCN1, likely in proximity to the DM site. In breast cancer cells, CCN1 can induce actin reorganization, formation of lamellipodia, and cell migration/invasion through the αV integrins/Rac1/ERK signaling axis; these CCN1-dependent activities can be effectively suppressed by YM1B. Our results also suggest that YM1B may exert its CCN1-blocking effect by perturbing the interaction of CCN1 with vitronectin and fibronectin, which are ligands of αV integrins and instrumental for integrin activation. This CCN1-specific mAb may open a new potential avenue for therapeutic intervention of breast cancer progression.

AB - CCN1, a secreted matrix-associated molecule, is involved in multiple cellular processes. Accumulating evidence supports that CCN1 plays an important role in tumorigenesis and progression of breast cancer. In this study, we have developed a novel CCN1 function-blocking monoclonal antibody (mAb), designated YM1B. YM1B binds to human CCN1 with high specificity, recognizing the native CCN1 structure with undisturbed disulfide linkages. Our analyses have mapped the YM1B recognition region to domain IV of CCN1, likely in proximity to the DM site. In breast cancer cells, CCN1 can induce actin reorganization, formation of lamellipodia, and cell migration/invasion through the αV integrins/Rac1/ERK signaling axis; these CCN1-dependent activities can be effectively suppressed by YM1B. Our results also suggest that YM1B may exert its CCN1-blocking effect by perturbing the interaction of CCN1 with vitronectin and fibronectin, which are ligands of αV integrins and instrumental for integrin activation. This CCN1-specific mAb may open a new potential avenue for therapeutic intervention of breast cancer progression.

KW - Breast cancer

KW - CCN1

KW - Cell migration

KW - Monoclonal antibody

KW - Rac

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JF - Biochemical and Biophysical Research Communications

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ER -

A novel anti-CCN1 monoclonal antibody suppresses Rac-dependent cytoskeletal reorganization and migratory activities in breast cancer cells

Abstract

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