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Cap2

Official Full Name
CAP, adenylate cyclase-associated protein, 2 (yeast)
Synonyms
CAP2; CAP, adenylate cyclase-associated protein, 2 (yeast); adenylyl cyclase-associated protein 2; CAP 2; 2810452G09Rik; zgc:73317; zgc:113089

Recent Research Progress

The cyclase-associated protein (CAP) consists of 474 to 551 amino acid residues and is an evolutionarily highly conserved protein between yeast and mammals. CAP exerts functions towards the activations of adenylyl cyclase and the mediating the dynamics of actin polymerization by binding to G-actin. Two homologs, CAP1 and CAP2, are present in higher eukaryotes. In rats, CAP2 transcripts are present in the testes, lungs and kidneys but not in the liver and spleen. During mouse embryonic development, CAP2 is detectable throughout the heart. Loss of CAP2 leads to cardiomyopathy based on data from CAP2 depletion causing dilated cardiomyopathy and various cardiac tests. In human cancer, CAP2 expression is different.

CAP2 and arrhythmias

CAP2 plays a major role in regulating the actin cytoskeleton. Studies have shown that loss of CAP2 results in marked electrophysiological disturbances including impaired sinus node function, conduction delays, and susceptibility to malignant arrhythmias. Structural changes in a gene trap approach (CAP2gt/gt) are associated with changes in myocardial connexin and fibrosis. In conclusion, the inactivation of CAP2 leads to a cardiomyopathy with associated electrophysiological alterations, primarily spontaneous and induced malignant ventricular arrhythmias.

CAP2 and HCC

Hepatocellular carcinoma (HCC) mortality ranks the second most common cause of cancer-related death in men, and the sixth in women. CAP2 is considered a potential diagnostic biomarker for early HCC. Current data indicated that a significant increase in CAP2 expression in HCC tissues, compared with non-tumor tissues. High CAP2 expression was significantly associated with differences in overall and disease-free survival. Prognostic significance was also effective in several subgroups of HCC patients. Thence, studies have shown that CAP2 was a promising biomarker for the prognosis of patients with HCC.

CAP2 and breast cancer

Breast cancer is the leading cause of cancer morbidity and mortality among women worldwide. Recent findings suggested that CAP2 was up-regulated in breast cancer and associated with expression of progesterone receptor (PR). Multivariate analysis showed that CAP2 might be an independent biomarker for predicting breast cancer prognosis and survival. Therefore, testing CAP2 protein levels may help to stratify new treatment strategies for patients and establish reasonable treatment selection criteria for breast cancer patients.

CAP2 and Malignant melanoma

Malignant melanoma is one of the deadly malignant tumors worldwide. Recently, studies have shown that CAP2 overexpression was a novel prognostic marker for malignant melanoma. CAP2 expression appears to increase gradually during tumor progression, and CAP2 overexpression was immunohistochemically detected even in some cases without lymph node metastasis. These findings suggest that analysis of CAP2 expression may be helpful in selecting adjuvant treatment for melanoma patients and providing prognostic information in addition to conventional clinicopathological predictive factors for overall survival.

In summary, current research indicates that abnormal expression of CAP2 is closely related to some myocardial diseases and cancer. However, there are few reports on the relationship between CAP2 and related tumors. Therefore, further study of the molecular mechanism of CAP2 involved in tumorigenesis will provide new targets and new insights for the diagnosis and treatment of related cancers.

References:

  1. K Kosmas, et al. CAP2 is a regulator of the actin cytoskeleton and its absence changes infiltration of inflammatory cells and contraction of wounds. European Journal of Cell Biology, 2015, 94: 32–45
  2. Florian Stöckigt, et al. Deficiency of cyclase-associated protein 2 promotes arrhythmias associated with connexin43 maldistribution and fibrosis. Arch Med Sci, 2016, 12(1): 188–198
  3. Fu J, et al. Increased Expression of CAP2 Indicates Poor Prognosis in Hepatocellular Carcinoma. Translational Oncology, 2015, 8: 400–406
  4. Chen A, et al. preliminary study of plasma cyclase-associated protein 2 as a novel biomarker for early stage and alpha-fetoprotein negative hepatocellular carcinoma patients. Clinics and Research in Hepatology and Gastroenterology, 2015, 39: 215—221
  5. Xu L, et al. Expression status of cyclase associated protein 2 as a prognostic marker for human breast cancer. Oncology Reports, 2016, 36: 1981-1988
  6. Masugi Y, et al. Overexpression of adenylate cyclase-associated protein 2 is a novel prognostic marker in malignant melanoma. Pathology International, 2015, 65: 627–634

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