4.4 Article

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

Journal

CURRENT ONCOLOGY
Volume 28, Issue 6, Pages 4972-4985

Publisher

MDPI
DOI: 10.3390/curroncol28060417

Keywords

breast cancer; CCN proteins; tumorigenesis; therapeutic advances; prospects

Categories

Funding

  1. Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2020R1I1A2066868]
  2. National Research Foundation of Korea (NRF) - Korea government (MSIT) [2020R1A5A2019413]
  3. Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HF20C0038]
  4. National Research Foundation [2020R1I1A1A01072879, 2015H1D3A1062189]
  5. Ministry of Science and ICT through the National Research Foundation [2020H1D3A2A02110924]

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CCNs are a specific type of matricellular protein that play essential roles in various biological processes such as cell adhesion, angiogenesis, and tumorigenesis in vertebrates. Different members of the CCN family may have either favorable or unfavorable associations with breast cancer. Recent studies have revealed the dual nature of tumor inhibition and promotion for certain CCNs in breast cancer.
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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