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Evaluation of the Interplay Between the Complement Protein C1q and Hyaluronic Acid in Promoting Cell Adhesion
Published on: June 15, 2019
Interactome analysis reveals that C1QBP (complement component 1, q subcomponent binding protein) is associated with
Xiaofang Zhang1, Fei Zhang, Lin Guo
1Research Center of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China;
Insights
Complement component 1, q subcomponent binding protein (C1QBP) regulates cancer cell migration and metastasis. This study identifies C1QBP as a novel therapeutic target for breast cancer treatment.
Area of Science:
- Molecular Biology
- Proteomics
- Cancer Research
Background:
- Complement component 1, q subcomponent binding protein (C1QBP) is a ubiquitous protein involved in diverse cellular functions.
- Understanding C1QBP's biological roles, particularly in cancer, requires detailed interactome analysis.
Purpose of the Study:
- To identify C1QBP interacting proteins and construct its interactome network.
- To investigate the role of C1QBP in cancer cell migration and metastasis.
- To evaluate C1QBP as a potential therapeutic target for breast cancer.
Main Methods:
- Proteomics analysis using an improved sample preparation and mass spectrometry strategy.
- High-speed centrifugation, formaldehyde labeling, and 2D-reverse-phase liquid chromatography.
- In vitro assays for cell chemotaxis and in vivo studies using a mouse model of breast cancer metastasis.
Main Results:
- Identified 187 C1QBP interacting proteins and built a highly connected interactome network.
- Demonstrated that C1QBP regulates protein kinase C ζ activity and modulates EGF-induced cancer cell chemotaxis.
- Confirmed C1QBP's essential role in breast cancer metastasis and its overexpression in human breast cancer tissues, correlating with advanced stages.
Conclusions:
- C1QBP is a novel regulator of cancer cell metastasis.
- C1QBP's involvement in cell migration and its overexpression in breast cancer highlight its potential as a therapeutic target.
Abstract:
The complement component 1, q subcomponent binding protein (C1QBP/p32/HABP1) is a ubiquitously expressed and multicompartmental cellular protein involved in various biological processes. In order to further understand its biological functions, we conducted proteomics analysis of its interactome in this study. An improved sample preparation and mass spectrometric identification strategy was developed combining high-speed centrifugation, formaldehyde labeling, and two-dimensional reverse-phase liquid chromatography. Using this approach, we identified 187 interacting proteins and constructed a highly connected interacting network for C1QBP. Moreover, we explored the interaction between C1QBP and protein kinase C ζ, a key regulator of cell polarity and migration. The results indicated that C1QBP regulated the activity of protein kinase C ζ and modulated EGF-induced cancer cell chemotaxis. In addition, C1QBP was required for breast cancer metastasis in a severe combined immunodeficiency mouse model. Furthermore, C1QBP was observed to be overexpressed in breast cancer tissues, and its expression level was closely linked with distant metastasis and TNM stages. In summary, C1QBP was identified as a novel regulator of cancer metastasis that may serve as a therapeutic target for breast cancer treatment.
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