CCN Family Proteins in Cancer: Insight Into Their Structures and Coordination Role in Tumor Microenvironment

Jia, Qingan; Xu, Binghui; Zhang, Yaoyao; Ali, Arshad; Liao, Xia

doi:10.3389/fgene.2021.649387

Cited by 27 publications

(23 citation statements)

References 152 publications

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“…Currently, the tumor microenvironment (TME) makes a significant impact on malignancies ( Bi et al, 2020 ; Jia et al, 2021 ; Li et al, 2021 ). As a major component of TME, CAF has multiple pro-tumorigenic functions during tumorigenesis ( Yang W et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analyses of PDHA1 that serves as a predictive biomarker for immunotherapy response in cancer

et al. 2022

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Recent studies have proposed that pyruvate dehydrogenase E1 component subunit alpha (PDHA1), a cuproptosis-key gene, is crucial to the glucose metabolism reprogram of tumor cells. However, the functional roles and regulated mechanisms of PDHA1 in multiple cancers are largely unknown. The Cancer Genome Atlas (TCGA), GEPIA2, and cBioPortal databases were utilized to elucidate the function of PDHA1 in 33 tumor types. We found that PDHA1 was aberrantly expressed in most cancer types. Lung adenocarcinoma (LUAD) patients with high PDHA1 levels were significantly correlated with poor prognosis of overall survival (OS) and first progression (FP). Kidney renal clear cell carcinoma (KIRC) patients with low PDHA1 levels displayed poor OS and disease-free survival (DFS). However, for stomach adenocarcinoma (STAD), the downregulated PDHA1 expression predicted a good prognosis in patients. Moreover, we evaluated the mutation diversity of PDHA1 in cancers and their association with prognosis. We also analyzed the protein phosphorylation and DNA methylation of PDHA1 in various tumors. The PDHA1 expression was negatively correlated with tumor-infiltrating immune cells, such as myeloid dendritic cells (DCs), B cells, and T cells in pan-cancers. Mechanically, we used single-cell sequencing to discover that the PDHA1 expression had a close link with several cancer-associated signaling pathways, such as DNA damage, cell invasion, and angiogenesis. At last, we conducted a co-expressed enrichment analysis and showed that aberrantly expressed PDHA1 participated in the regulation of mitochondrial signaling pathways, including oxidative phosphorylation, cellular respiration, and electron transfer activity. In summary, PDHA1 could be a prognostic and immune-associated biomarker in multiple cancers.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analyses of PDHA1 that serves as a predictive biomarker for immunotherapy response in cancer

et al. 2022

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“…The six different members of the CCN gene family includes Cyr61 (CCN1), CTGF (CCN2), NOV (CCN3), WISP-1 (CCN4), WISP-2 (CCN5), and WISP-3 (CCN6) [ 24 ]. Biological functions, such as cell growth, ECM regulation, cell adhesion, migration, wound healing and angiogenesis, and diseases including fibrosis, cancer and vascular diseases are mostly regulated by the expression of the CCN gene family.…”

Section: Ccn Gene Familymentioning

confidence: 99%

“…The CCN family proteins contain six members that may regulate the tumor microenvironment. Numerous studies have suggested CCN family proteins can be an effective target in treating breast cancer (see Figure 2 ) [ 24 ].…”

Section: Pharmacological Advances In Treating Breast Cancer By Targeting Ccn Proteinsmentioning

confidence: 99%

Potential Role of CCN Proteins in Breast Cancer: Therapeutic Advances and Perspectives

et al. 2021

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CCNs are a specific type of matricellular protein, which are essential signaling molecules, and play multiple roles in multicellular eukaryotes. This family of proteins consists of six separate members, which exist only in vertebrates. The architecture of CCN proteins is multi-modular comprising four distinct modules. CCN Proteins achieve their primary functional activities by binding with several integrin7 receptors. The CCN family has been linked to cell adhesion, chemotaxis and migration, mitogenesis, cell survival, angiogenesis, differentiation, tumorigenesis, chondrogenesis, and wound healing, among other biological interactions. Breast cancer is the most commonly diagnosed cancer worldwide and CCN regulated breast cancer stands at the top. A favorable or unfavorable association between various CCNs has been reported in patients with breast carcinomas. The pro-tumorigenic CCN1, CCN2, CCN3, and CCN4 may lead to human breast cancer, although the anti-tumorigenic actions of CCN5 and CCN6 are also present. Several studies have been conducted on CCN proteins and cancer in recent years. CCN1 and CCN3 have been shown to exhibit a dual nature of tumor inhibition and tumor suppression to some extent in quiet recent time. Pharmacological advances in treating breast cancer by targeting CCN proteins are also reported. In our study, we intend to provide an overview of these research works while keeping breast cancer in focus. This information may facilitate early diagnosis, early prognosis and the development of new therapeutic strategies.

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“…CCN3/NOV is also known for promoting angiogenesis by supporting endothelial cell migration, adhesion, and survival [ 31 ]. CCN4/WISP-1 and CCN5/WISP-2 have roles in metabolic disorders involving glucose homeostasis, such as insulin resistance, diabetes, and obesity [ 16 , 32 , 33 ], and have been associated with the development and regulation of different types of cancers [ 34 , 35 , 36 ]. CCN6/WISP-3, on the other hand, has been shown to work as a tumor suppressor blocking breast cancer development [ 37 , 38 , 39 ].…”

Section: The Ccn Family Of Matricellular Proteinsmentioning

confidence: 99%

Role of Matricellular CCN Proteins in Skeletal Muscle: Focus on CCN2/CTGF and Its Regulation by Vasoactive Peptides

Rebolledo

Acuña

Brandan

2021

IJMS

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The Cellular Communication Network (CCN) family of matricellular proteins comprises six proteins that share conserved structural features and play numerous biological roles. These proteins can interact with several receptors or soluble proteins, regulating cell signaling pathways in various tissues under physiological and pathological conditions. In the skeletal muscle of mammals, most of the six CCN family members are expressed during embryonic development or in adulthood. Their roles during the adult stage are related to the regulation of muscle mass and regeneration, maintaining vascularization, and the modulation of skeletal muscle fibrosis. This work reviews the CCNs proteins’ role in skeletal muscle physiology and disease, focusing on skeletal muscle fibrosis and its regulation by Connective Tissue Growth factor (CCN2/CTGF). Furthermore, we review evidence on the modulation of fibrosis and CCN2/CTGF by the renin-angiotensin system and the kallikrein-kinin system of vasoactive peptides.

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CCN Family Proteins in Cancer: Insight Into Their Structures and Coordination Role in Tumor Microenvironment

Cited by 27 publications

References 152 publications

Comprehensive analyses of PDHA1 that serves as a predictive biomarker for immunotherapy response in cancer

Comprehensive analyses of PDHA1 that serves as a predictive biomarker for immunotherapy response in cancer

Potential Role of CCN Proteins in Breast Cancer: Therapeutic Advances and Perspectives

Role of Matricellular CCN Proteins in Skeletal Muscle: Focus on CCN2/CTGF and Its Regulation by Vasoactive Peptides

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