Macrophage Capping Protein CapG Is a Putative Oncogene Involved in Migration and Invasiveness in Ovarian Carcinoma

Abstract

The actin binding protein CapG modulates cell motility by interacting with the cytoskeleton. CapG is associated with tumor progression in different nongynecologic tumor entities and overexpression in breast cancer cell lines correlates with a more invasive phenotype in vitro. Here, we report a significant CapG overexpression in 18/47 (38%) of ovarian carcinomas (OC) analyzed by qRealTime-PCR analyses. Functional analyses in OC cell lines through siRNA mediated CapG knockdown and CapG overexpression showed CapG-dependent cell migration and invasiveness. A single nucleotide polymorphism rs6886 inside the CapG gene was identified, affecting a CapG phosphorylation site and thus potentially modifying CapG function. The minor allele frequency (MAF) of SNP rs6886 (c.1004A/G) was higher and the homozygous (A/A, His335) genotype was significantly more prevalent in patients with fallopian tube carcinomas (50%) as in controls (10%). With OC being one of the most lethal cancer diseases, the detection of novel biomarkers such as CapG could reveal new diagnostic and therapeutic targets. Moreover, in-depth analyses of SNP rs6886 related to FTC and OC will contribute to a better understanding of carcinogenesis and progression of OC.

Application of post-genomic techniques in dog cancer research

“…75 Remarkably, this paper was the first to identify MCP as cancer biomarker. Other studies on different human malignancies [76][77][78][79][80] validated MCP as a cancer biomarker, further supporting the use of dogs as useful models for human cancer. Studies on the serum proteome changes of canine lymphoma have been carried out by combining ion exchange chromatography and surface-enhanced laser desorption ionisation (SELDI) mass spectrometry.…”

Association of Macrophage Capping Protein (CAPG) Arg335 his Polymorphism and Cancer Susceptibility in the Elderly Japanese

“…As mentioned above, the causal role for CAPG in tumorigenesis has been extensively explored. In addition, recent study with a small sample size demonstrated a positive association of a CAPG variant with a rare fallopian tube tumor [21]. Along with the above evidence, we hypothesized that CAPG might be crucial for the development and progression of malignancy.…”

“…Recent evidence that CAPG p.R335H was associated with risk of fallopian tube carcinoma in a small case-control study promoted us to examine the effect of the SNV of CAPG on various cancers using large-sized autopsy cases [21]. Most previous reports demonstrated a positive association between cancer and CAPG protein expression [5][6][7][8][9][10][25][26][27][28][29].…”

“…Regarding the location of Arg335 allele, which is located in the surface of loop, this makes Arg335 allele is likely to be phosphorylated by PKC compare to His335 allele. Indeed, Glaser and colleagues described that CAPG protein (p.R335H) with histidine variant diminished the phosphorylation level of adjacent Ser337 by PKC [21]. Interestingly, a recent analysis of somatic mutations in tumors using TCGA database suggests that mutations in phosphosite flanking region are found in 89% of tumors [39].…”

Function of the macrophage‑capping protein in colorectal carcinoma

“…It has been reported that CapG is associated with invasion and metastasis in various types of malignancy (15)(16)(17). However, to the best of our knowledge, the effect of CapG in primary CRC was not investigated prior to the present study.…”