Damage-specific DNA-binding protein 2 (DDB2) was originally identified as a DNA damage recognition factor that facilitates global genomic nucleotide excision repair (GG-NER) in human cells. DDB2 also contributes to other essential biological processes such as chromatin remodeling, gene transcription, cell cycle regulation, and protein decay. Recently, the potential of DDB2 in the development and progression of various cancers has been described. DDB2 activity occurs at several stages of carcinogenesis including cancer cell proliferation, survival, epithelial to mesenchymal transition, migration and invasion, angiogenesis, and cancer stem cell formation. In this review, we focus on the current state of scientific knowledge regarding DDB2 biological effects in tumor development and the underlying molecular mechanisms. We also provide insights into the clinical consequences of DDB2 activity in cancers.
tumor-free omentum, indicating a niche for ovarian cancer cells toward omental metastasis. Conclusion Our data demonstrate that a2,6 sialylation on integrin a2 triggers ovarian cancer cell adhesion to metastatic sites. Therefore, blocking sialylation and integrin a2 may be a therapeutic target for preventing ovarian cancer metastasis in the future. Introduction Breast cancer (BC) remains the most prevalent female cancer in Egypt and worldwide. Microfibrillar-associated protein 5 (MFAP5) is a multifunctional glycoprotein. Although MFAP5 gene was among the genes that found globally expressed in human cancers, it had been only recently reported in few cancer research studies. Material and methods This is a retrospective study that has been conducted on 66 Egyptian patients who had invasive carcinoma of no special type (IC-NST). Immunohistochemical staining for MFAP5 was applied on the archival formalin-fixed paraffin-embedded blocks. Staining was assessed semiquantitatively and correlated with the available clinicopathological parameters and immunohistochemical subtypes of BC. Results and discussions MFAP5 epithelial cytoplasmic expression was observed in 89.4% (59/66) of cases. In contrast, nuclear expression was seen in normal breast lobules and premalignant lesions adjacent to tumours that also exhibited constant staining in myoepithelial layer. Statistical analysis of epithelial cytoplasmic expression revealed association of MFAP5 expression with tumour size (p=0.046), high histological grade (p=0.007), presence of lymph node (LN) metastasis (p=0.014), poor Nottingham Prognostic Index (NPI) (p=0.001), late stage (p=0.008), immunohistochemical subtypes of BC (p=0.018), and increased MVD using CD34 immunostianing (p=0.04). MFAP5 cytoplasmic expression was also observed in an adjacent DCIS component in 37/45 cases (82.2%). Conclusion This study showed that MFAP5 is a novel myoepithelial cell marker that appears to be up-regulated in duct epithelium in DCIS and IC-NST during tumourogenesis and that its cytoplasmic expression in invasive tumours seems to have a poor prognostic role manifested by its association with poor prognostic parameters such as high grade, late stage, lymph node invasion and increased MVD. PO-174
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