Binding blockade between TLN1 and integrin β1 represses triple-negative breast cancer
Background: Integrin family are known as key gears in focal adhesion for triple-negative breast cancer (TNBC) metastasis. However, the integrin independent factor TLN1 remains vague in TNBC. Methods: Bioinformatics analysis was performed based on TCGA database and Shengjing Hospital cohort. Western...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2022-03-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/68481 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850034054043271168 |
|---|---|
| author | Yixiao Zhang Lisha Sun Haonan Li Liping Ai Qingtian Ma Xinbo Qiao Jie Yang Hao Zhang Xunyan Ou Yining Wang Guanglei Chen Jinqi Xue Xudong Zhu Yu Zhao Yongliang Yang Caigang Liu |
| author_facet | Yixiao Zhang Lisha Sun Haonan Li Liping Ai Qingtian Ma Xinbo Qiao Jie Yang Hao Zhang Xunyan Ou Yining Wang Guanglei Chen Jinqi Xue Xudong Zhu Yu Zhao Yongliang Yang Caigang Liu |
| author_sort | Yixiao Zhang |
| collection | DOAJ |
| description | Background: Integrin family are known as key gears in focal adhesion for triple-negative breast cancer (TNBC) metastasis. However, the integrin independent factor TLN1 remains vague in TNBC.
Methods: Bioinformatics analysis was performed based on TCGA database and Shengjing Hospital cohort. Western blot and RT-PCR were used to detect the expression of TLN1 and integrin pathway in cells. A small-molecule C67399 was screened for blocking TLN1 and integrin β1 through a novel computational screening approach by targeting the protein-protein binding interface. Drug pharmacodynamics were determined through xenograft assay.
Results: Upregulation of TLN1 in TNBC samples correlates with metastasis and worse prognosis. Silencing TLN1 in TNBC cells significantly attenuated the migration of tumour cells through interfering the dynamic formation of focal adhesion with integrin β1, thus regulating FAK-AKT signal pathway and epithelial-mesenchymal transformation. Targeting the binding between TLN1 and integrin β1 by C67399 could repress metastasis of TNBC.
Conclusions: TLN1 overexpression contributes to TNBC metastasis and C67399 targeting TLN1 may hold promise for TNBC treatment.
Funding: This study was supported by grants from the National Natural Science Foundation of China (No. 81872159, 81902607, 81874301), Liaoning Colleges Innovative Talent Support Program (Name: Cancer Stem Cell Origin and Biological Behaviour), Outstanding Scientific Fund of Shengjing Hospital (201803), and Outstanding Young Scholars of Liaoning Province (2019-YQ-10). |
| format | Article |
| id | doaj-art-a08fb54dc9af4d798569619ba10ec192 |
| institution | DOAJ |
| issn | 2050-084X |
| language | English |
| publishDate | 2022-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-a08fb54dc9af4d798569619ba10ec1922025-08-20T02:57:57ZengeLife Sciences Publications LtdeLife2050-084X2022-03-011110.7554/eLife.68481Binding blockade between TLN1 and integrin β1 represses triple-negative breast cancerYixiao Zhang0Lisha Sun1https://orcid.org/0000-0002-4095-5026Haonan Li2Liping Ai3Qingtian Ma4Xinbo Qiao5https://orcid.org/0000-0002-6759-921XJie Yang6Hao Zhang7Xunyan Ou8Yining Wang9Guanglei Chen10Jinqi Xue11Xudong Zhu12Yu Zhao13Yongliang Yang14Caigang Liu15https://orcid.org/0000-0003-3729-2839Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang, China; Innovative Cancer Drug Research and Development Engineering Center of Liaoning Province, Shenyang, ChinaSchool of Bioengineering, Dalian University of Technology, Dalian, ChinaCancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang, ChinaCancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang, ChinaCancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang, ChinaCancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang, ChinaCancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang, ChinaDepartment of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, United StatesDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang, China; School of Bioengineering, Dalian University of Technology, Dalian, ChinaDepartment of Oncology, Shengjing Hospital of China Medical University, Shenyang, China; Cancer Stem Cell and Translational Medicine Laboratory, Shengjing Hospital of China Medical University, Shenyang, China; Innovative Cancer Drug Research and Development Engineering Center of Liaoning Province, Shenyang, ChinaBackground: Integrin family are known as key gears in focal adhesion for triple-negative breast cancer (TNBC) metastasis. However, the integrin independent factor TLN1 remains vague in TNBC. Methods: Bioinformatics analysis was performed based on TCGA database and Shengjing Hospital cohort. Western blot and RT-PCR were used to detect the expression of TLN1 and integrin pathway in cells. A small-molecule C67399 was screened for blocking TLN1 and integrin β1 through a novel computational screening approach by targeting the protein-protein binding interface. Drug pharmacodynamics were determined through xenograft assay. Results: Upregulation of TLN1 in TNBC samples correlates with metastasis and worse prognosis. Silencing TLN1 in TNBC cells significantly attenuated the migration of tumour cells through interfering the dynamic formation of focal adhesion with integrin β1, thus regulating FAK-AKT signal pathway and epithelial-mesenchymal transformation. Targeting the binding between TLN1 and integrin β1 by C67399 could repress metastasis of TNBC. Conclusions: TLN1 overexpression contributes to TNBC metastasis and C67399 targeting TLN1 may hold promise for TNBC treatment. Funding: This study was supported by grants from the National Natural Science Foundation of China (No. 81872159, 81902607, 81874301), Liaoning Colleges Innovative Talent Support Program (Name: Cancer Stem Cell Origin and Biological Behaviour), Outstanding Scientific Fund of Shengjing Hospital (201803), and Outstanding Young Scholars of Liaoning Province (2019-YQ-10).https://elifesciences.org/articles/68481triple-negative breast cancerTLN1cell adhesionsmall molecule |
| spellingShingle | Yixiao Zhang Lisha Sun Haonan Li Liping Ai Qingtian Ma Xinbo Qiao Jie Yang Hao Zhang Xunyan Ou Yining Wang Guanglei Chen Jinqi Xue Xudong Zhu Yu Zhao Yongliang Yang Caigang Liu Binding blockade between TLN1 and integrin β1 represses triple-negative breast cancer eLife triple-negative breast cancer TLN1 cell adhesion small molecule |
| title | Binding blockade between TLN1 and integrin β1 represses triple-negative breast cancer |
| title_full | Binding blockade between TLN1 and integrin β1 represses triple-negative breast cancer |
| title_fullStr | Binding blockade between TLN1 and integrin β1 represses triple-negative breast cancer |
| title_full_unstemmed | Binding blockade between TLN1 and integrin β1 represses triple-negative breast cancer |
| title_short | Binding blockade between TLN1 and integrin β1 represses triple-negative breast cancer |
| title_sort | binding blockade between tln1 and integrin β1 represses triple negative breast cancer |
| topic | triple-negative breast cancer TLN1 cell adhesion small molecule |
| url | https://elifesciences.org/articles/68481 |
| work_keys_str_mv | AT yixiaozhang bindingblockadebetweentln1andintegrinb1repressestriplenegativebreastcancer AT lishasun bindingblockadebetweentln1andintegrinb1repressestriplenegativebreastcancer AT haonanli bindingblockadebetweentln1andintegrinb1repressestriplenegativebreastcancer AT lipingai bindingblockadebetweentln1andintegrinb1repressestriplenegativebreastcancer AT qingtianma bindingblockadebetweentln1andintegrinb1repressestriplenegativebreastcancer AT xinboqiao bindingblockadebetweentln1andintegrinb1repressestriplenegativebreastcancer AT jieyang bindingblockadebetweentln1andintegrinb1repressestriplenegativebreastcancer AT haozhang bindingblockadebetweentln1andintegrinb1repressestriplenegativebreastcancer AT xunyanou bindingblockadebetweentln1andintegrinb1repressestriplenegativebreastcancer AT yiningwang bindingblockadebetweentln1andintegrinb1repressestriplenegativebreastcancer AT guangleichen bindingblockadebetweentln1andintegrinb1repressestriplenegativebreastcancer AT jinqixue bindingblockadebetweentln1andintegrinb1repressestriplenegativebreastcancer AT xudongzhu bindingblockadebetweentln1andintegrinb1repressestriplenegativebreastcancer AT yuzhao bindingblockadebetweentln1andintegrinb1repressestriplenegativebreastcancer AT yongliangyang bindingblockadebetweentln1andintegrinb1repressestriplenegativebreastcancer AT caigangliu bindingblockadebetweentln1andintegrinb1repressestriplenegativebreastcancer |