Input of microenvironmental regulation on colorectal cancer: Role of the CCN family

Colorectal cancer (CRC) is a major health problem causing significant morbidity and mortality. Previous results from various studies indicate that CRC tumorigenicity encompasses tumor microenvironment, emphasizing the complex interacting network between cancer cells and nearby host cells, which triggers diverse signaling pathways to promote the growth and spread of cancer cells. The CCN family proteins share a uniform modular structure, mediating a variety of physiological functions, including proliferation, apoptosis, migration, adhesion, differentiation, and survival. Furthermore, CCN proteins are also involved in CRC initiation and development. Many studies have shown that CCN members, such as CCN1, CCN2, CCN3, Wnt-induced secreted protein (WISP)-1, WISP-2, and WISP-3, are dysregulated in CRC, which implies potential diagnostic markers or therapeutic targets clinically. In this review, we summarize the research findings on the role of CCN family proteins in CRC initiation, development, and progression, highlighting their potential for diagnosis, prognosis, and therapeutic application.