The C1q Receptors: Focus on gC1qR/p33 (C1qBP, p32, HABP-1)1

Ghebrehiwet, Berhane; Geisbrecht, Brian V.; Xu, Xin; Savitt, Anne G.; Peerschke, Ellinor I.B.

doi:10.1016/j.smim.2019.101338

Cited by 64 publications

(97 citation statements)

References 99 publications

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“…However, little is known about the molecular mechanism of C1QBP in metabolism and progression of RCC. C1QBP plays critical roles in mitochondria protein synthesis, maintenance of oxidative phosphorylation, and tumor metabolism reprograming, suggesting the importance of C1QBP in metabolism [5,11]. In present study, we applied metabolomics to analyze differential metabolites in C1QBP overexpression RCC cells among 200 main metabolites.…”

Section: Discussionmentioning

confidence: 97%

“…Given the numerous important roles in multiple disease, C1QBP has now become a potential target for the development of monoclonal antibody-based and/or small molecule-based therapies [5]. However, little is known about the molecular mechanism of C1QBP in metabolism and progression of RCC.…”

Section: Discussionmentioning

confidence: 99%

“…Complement component 1 Q subcomponent binding protein (C1QBP) also known as HABP1, SF2p32, gC1qR, p32 is a highly conservative and multi-functional protein that ubiquitously distributes in the mitochondria matrix, cell membrane as well as in the secreted form, and it plays an important role in in ammation, infection, and cancer [5]. Studies have shown that C1QBP is overexpressed in malignant cells, e. g. breast, colon, and gastric cancers, in which it promotes various cellular processes, including cell survival, growth, apoptosis, and metastasis [5][6][7][8]. Interestingly, in our previous study, unlike other malignancies, C1QBP showed diminished expression in RCC compared with the corresponding paratumor tissues and suppressed adhesion and metastasis of RCC [9].…”

Section: Introductionmentioning

confidence: 99%

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C1QBP regulates apoptosis of renal cell carcinoma via modulating xanthine dehydrogenase (XDH) mediated ROS generation

Wang¹,

Cui²,

Wang³

et al. 2020

Preprint

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Background Complement component 1 Q subcomponent binding protein (C1QBP) is a multifunctional protein and plays a vital role in the progression and metabolism of cancer. Our previous study has revealed that the low expression of C1QBP in renal cell carcinoma (RCC) and knockdown of C1QBP promotes the adhesion and invasion of RCC cells. However, its functions in the metabolism, oxidative stress and apoptosis of RCC cells have not yet been explored. Methods Metabolomics assay was applied to investigate the role of C1QBP in RCC metabolism. C1QBP knockdown and overexpression cells were established via lentiviral infection and subjected to apoptosis and ROS assay in vitro. RNA stability assay and pre-mRNA detection were applied to characterize the mechanism of C1QBP regulating XDH transcription. In vivo, orthotopic tumor xenografts assay was performed to investigate the role of C1QBP progression. Results Metabolomics investigations revealed that C1QBP dramatically diminished the hypoxanthine content in RCC cells. C1QBP promoted the mRNA and protein expression of hypoxanthine catabolic enzyme xanthine dehydrogenase (XDH). Meanwhile, C1QBP regulated the expression of XDH gene at the pre-transcriptional level by regulating XDH transcriptional stimulators IL-6, TNF-α and IFN-γ. Moreover, the expression of C1QBP and XDH was lower in RCC tumors compared with the para-tumor normal tissues, and their down-regulation was associated with higher levels of Fuhrman grade. In RCC cells, C1QBP significantly increased produces reactive oxygen species (ROS) levels, apoptosis, and the expression of apoptotic proteins cleaved caspase-3 and bax/bcl2 via regulating XDH.Conclusions C1QBP promotes the catabolism of hypoxanthine and elevates the apoptosis of RCC cells by modulating XDH-mediated ROS generation.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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C1QBP regulates apoptosis of renal cell carcinoma via modulating xanthine dehydrogenase (XDH) mediated ROS generation

Wang¹,

Cui²,

Wang³

et al. 2020

Preprint

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“…The therapeutic murine monoclonal antibody (60.11) (IgG) is directed against N-terminal amino acids 76-93 of human gC1qR, and specifically inhibits C1q binding [27,28]. Surface plasmon resonance studies estimate the binding affinity of 60.11 for gC1qR at 67 nM (Appendix A).…”

Section: Antibody Productionmentioning

confidence: 99%

Anti gC1qR/p32/HABP1 Antibody Therapy Decreases Tumor Growth in an Orthotopic Murine Xenotransplant Model of Triple Negative Breast Cancer

et al. 2020

Self Cite

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gC1qR is highly expressed in breast cancer and plays a role in cancer cell proliferation. This study explored therapy with gC1qR monoclonal antibody 60.11, directed against the C1q binding domain of gC1qR, in a murine orthotopic xenotransplant model of triple negative breast cancer. MDA231 breast cancer cells were injected into the mammary fat pad of athymic nu/nu female mice. Mice were segregated into three groups (n = 5, each) and treated with the vehicle (group 1) or gC1qR antibody 60.11 (100 mg/kg) twice weekly, starting at day 3 post-implantation (group 2) or when the tumor volume reached 100 mm3 (group 3). At study termination (d = 35), the average tumor volume in the control group measured 895 ± 143 mm3, compared to 401 ± 48 mm3 and 701 ± 100 mm3 in groups 2 and 3, respectively (p < 0.05). Immunohistochemical staining of excised tumors revealed increased apoptosis (caspase 3 and TUNEL staining) in 60.11-treated mice compared to controls, and decreased angiogenesis (CD31 staining). Slightly decreased white blood cell counts were noted in 60.11-treated mice. Otherwise, no overt toxicities were observed. These data are the first to demonstrate an in vivo anti-tumor effect of 60.11 therapy in a mouse model of triple negative breast cancer.

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“…Complement factor C1q consists of collagen-like [cC1q] and globular head [gC1q] regions that bind receptors cC1qR and gC1qR, respectively. The activation of both of these receptors on endothelial cells contributes to angiogenesis (Ghebrehiwet et al, 2019). gC1qR also binds factor XII and high molecular weight kininogen in initiating the kallikrein-kinin system and the secondary hemostasis intrinsic pathway (Kaira et al, 2020).…”

Section: Endothelial Cellsmentioning

confidence: 99%

COVID-19 Usurps Host Regulatory Networks

2020

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 binds the angiotensin-converting enzyme 2 (ACE2) on the cell surface and this complex is internalized. ACE2 serves as an endogenous inhibitor of inflammatory signals associated with four major regulator systems: the renin-angiotensin-aldosterone system (RAAS), the complement system, the coagulation cascade, and the kallikrein-kinin system (KKS). Understanding the pathophysiological effects of SARS-CoV-2 on these pathways is needed, particularly given the current lack of proven, effective treatments. The vasoconstrictive, prothrombotic and pro-inflammatory conditions induced by SARS-CoV-2 can be ascribed, at least in part, to the activation of these intersecting physiological networks. Moreover, patients with immune deficiencies, hypertension, diabetes, coronary heart disease, and kidney disease often have altered activation of these pathways, either due to underlying disease or to medications, and may be more susceptible to SARS-CoV-2 infection. Certain characteristic COVID-associated skin, sensory, and central nervous system manifestations may also be linked to viral activation of the RAAS, complement, coagulation, and KKS pathways. Pharmacological interventions that target molecules along these pathways may be useful in mitigating symptoms and preventing organ or tissue damage. While effective anti-viral therapies are critically needed, further study of these pathways may identify effective adjunctive treatments and patients most likely to benefit.

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The C1q Receptors: Focus on gC1qR/p33 (C1qBP, p32, HABP-1)1

Cited by 64 publications

References 99 publications

C1QBP regulates apoptosis of renal cell carcinoma via modulating xanthine dehydrogenase (XDH) mediated ROS generation

C1QBP regulates apoptosis of renal cell carcinoma via modulating xanthine dehydrogenase (XDH) mediated ROS generation

Anti gC1qR/p32/HABP1 Antibody Therapy Decreases Tumor Growth in an Orthotopic Murine Xenotransplant Model of Triple Negative Breast Cancer

COVID-19 Usurps Host Regulatory Networks

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