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Cap1

Official Full Name
CAP, adenylate cyclase-associated protein 1 (yeast)
Background
The protein encoded by this gene is related to the S. cerevisiae CAP protein, which is involved in the cyclic AMP pathway. The human protein is able to interact with other molecules of the same protein, as well as with CAP2 and actin. Alternatively spliced transcript variants have been identified.
Synonyms
CAP1; CAP, adenylate cyclase-associated protein 1 (yeast); adenylyl cyclase-associated protein 1; CAP; Adenylyl cyclase associated protein 1; CAP1 PEN; CAP 1; CAP1-PEN; fj98f01; zgc:63872; wu:fj98f01; Cap1 CAP, adenylate cyclase-associated protein 1

Recent Research Progress

Cyclase-Associated Protein 1 (CAP1), a member of the CAP family in mammalian cells, was first identified as a component of the yeast adenylate cyclase complex and is conserved in all eukaryotes. CAP1 regulates the actin filament and Ras/Cyclic Adenosine monophosphate (cAMP) pathways in yeast and has been found to play a role in cell movement and the development of certain types of cancer.

CAP1 and breast cancer

Recent studies have found that CAP1 exerts a cell type-dependent function in the invasiveness of breast cancer cells. Depletion of CAP1 in metastatic MDA-MB-231 (human breast cancer cells) and BT-549 (human breast duct cancer cells) cancer cells stimulates metastatic potential, whereas it actually inhibits it in non-metastatic MCF-7 (human breast cancer cell line) cancer cells or normal cells. Importantly, the critical role of extracellular regulated protein kinases (ERK)-centric signaling in mediating CAP1 function has been identified. Fluorescent mutants of CAP1 at the S307/S309 regulatory site have a detrimental effect on the invasiveness and proliferation of CAP1 knockdown cells, suggesting that CAP1 may mediate upstream cellular signals to control both functions. These novel mechanisms of insight may ultimately open the way to strategies for CAP1 in breast cancer treatment, tailored to a specific type of highly diverse disease.

CAP1 and glioma

Glioma is the most common primary intracranial tumor, composed of neuroectoderm, and is therefore also known as neuroectoderm or neuroepithelial tumor, accounting for 50% of primary intracranial tumors. As the most invasive glioma type, glioblastoma multiforme (GBM) is a grade IV histological malignancy according to World Health Organization (WHO) classification with a median patient survival period of 12-14 months. Recent studies have found that CAP1 was overexpressed in that noted in the tumor adjacent normal brain tissues, and increased staining of CAP1 was found to be associated with the WHO stage. Furthermore, it has been discovered that knockdown of CAP1 by specific RNA interference significantly inhibits cell growth and leads to down-regulation of the proliferation markers proliferating cell nuclear antigen (PCNA) and cyclin A. Further studies have demonstrated that knockdown of CAP1 inhibited cell metastatic abilities by down-regulating N-cadherin and vimentin and up-regulating E-cadherin. These findings revealed a significant increase in CAP1 expression in human gliomas, and down-regulation of CAP1 in tumors could be treated as a glioma patient.

CAP1 and EOC

Epithelial ovarian cancer (EOC) is one of the most common ovarian tumors and is the leading cause of death in gynecologic malignancies. Despite the rapid development of surgery and chemotherapy, the 5-year survival rate of EOC patients remains at about 30-50% due to the lack of effective early diagnosis. Hua et al. investigated the expression of the CAP1 gene in human EOC. Western blot analysis and immunohistochemistry were performed using EOC tissue samples, and the results showed that CAP1 expression increased with increasing EOC grade. However, in normal ovarian tissue samples, almost no CAP1 expression was detected. Using Pearson's χ2 test, it was demonstrated that CAP1 expression was associated with histological grade and Ki-67 expression. Kaplan-Meier analysis revealed that higher CAP1 expression in EOC patients was associated with a poorer prognosis. In an in vitro experiment using HO-8910 EOC cells, siRNA was used to knock down the expression of CAP1. The results showed that loss of CAP1 expression inhibited cell cycle progression. These findings indicate that high expression of CAP1 is involved in the pathogenesis of EOC, and down-regulation of CAP1 in tumor cells may be a therapeutic target for the treatment of EOC patients.

CAP1 and NSCLC

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancers, and 5-year survival rates for patients with metastatic NSCLC are<10%. Brain metastasis (BM) occurs frequently in patients with NSCLC. The study found that CAP1 protein content and immunoreactivity were significantly increased in BM specimens compared to other metastatic specimens. The Survival analysis showed that CAP1 overexpression was significantly associated with survival. CAP1 has been shown to be involved in the BM of NSCLC, and elevated levels of CAP1 expression may indicate a poor prognosis in BM patients. The CAP1 molecular model can be used to predict the risk of BM in NSCLC.

In summary, due to the pivotal role of actin filament recombination in cell migration and the regulation of CAP1 in actin filament recombination, there is increasing evidence that CAP1 is associated with a variety of cancers. Therefore, further study of the mechanism of action of CAP1 in various cancers will provide new directions and new insights for the diagnosis and treatment of cancer.

References:

  1. Zhang Haitao, et al. CAP1 (Cyclase-Associated Protein 1) Exerts Distinct Functions in the Proliferation and Metastatic Potential of Breast Cancer Cells Mediated by ERK. Scientific Reports, 2016, 6:2593
  2. Fan Yuechao, et al. Overexpression of CAP1 and its significance in tumor cell proliferation, migration and invasion in glioma. Oncology Reports, 2016, 36: 1619-1625
  3. Bao Z, et al. High expression of adenylate cyclase-associated protein 1 accelerates the proliferation, migration and invasion of neural glioma cells. Pathology Research and Practice, 212(4): 264-273
  4. Hua Minhui, et al. CAP1 is overexpressed in human epithelial ovcancer and promotes cell proliferation. International Journal Of Molecular Medicine, 2015, 35: 941-949
  5. Xi Shuanshuan, et al. Overexpression of adenylate cyclase-associated protein 1 may predict brain metastasis in non-small cell lung cancer. Oncology Reports, 2015, 33: 363-371

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