Emerging roles of CCM genes during tumorigenesis with potential application as novel biomarkers across major types of cancers

Abou‑Fadel,Johnathan; Qu,Yanchun; Gonzalez,Elias M.; Smith,Mark; Zhang,Jun

doi:10.3892/or.2020.7550

Emerging roles of CCM genes during tumorigenesis with potential application as novel biomarkers across major types of cancers

Authors:
- Johnathan Abou‑Fadel
- Yanchun Qu
- Elias M. Gonzalez
- Mark Smith
- Jun Zhang
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Affiliations: Department of Molecular and Translational Medicine (MTM), Texas Tech University Health Science Center El Paso, El Paso, TX 79905, USA
Published online on: March 18, 2020 https://doi.org/10.3892/or.2020.7550
Pages: 1945-1963
Copyright: © Abou‑Fadel et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cerebral cavernous malformations (CCMs) are microvascular anomalies in the brain that result in increased susceptibility to stroke. Three genes have been identified as causes of CCMs: cerebral cavernous malformations 1 [(CCM1) also termed Krev interaction trapped 1 (KRIT1)], cerebral cavernous malformation 2 [(CCM2) also termed MGC4607] and cerebral cavernous malformation 3 [(CCM3) also termed programmed cell death 10 (PDCD10)]. It has been demonstrated that both CCM1 and CCM3 bind to CCM2 to form a CCM signaling complex (CSC) with which to modulate multiple signaling cascades. CCM proteins have been reported to play major roles in microvascular angiogenesis in human and animal models. However, CCM proteins are ubiquitously expressed in all major tissues, suggesting an unseen broader role of the CSC in biogenesis. Recent evidence suggests the possible involvement of the CSC complex during tumorigenesis; however, studies concerning this aspect are limited. This is the first report to systematically investigate the expression patterns of CCM proteins in major human tumors using real‑time quantitative PCR, RNA‑fluorescence in situ hybridization, immunohistochemistry and multicolor immunofluorescence imaging. Our data demonstrated that differential expression patterns of the CSC complex are correlated with certain types and grades of major human cancers, indicating the potential application of CCM genes as molecular biomarkers for clinical oncology. Our data strongly suggest that more efforts are needed to elucidate the role of the CSC complex in tumorigenesis, which may have enormous clinical potential for cancer diagnostic, prognostic and therapeutic applications.

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