Reduced expression of lamin A/C was detected in colon cancer (37), small cell lung cancer (38), leukemias and lymphomas (39,40). serves prominent functions in resistance to the excessive DNA damage that destabilizes the genome and promotes cancer development, and these functions of SUN2 are Isepamicin critical for evading initiation of malignancy. Additionally, increasing evidence has exhibited that SUN2 is involved in maintaining cell nuclear structure and appears to be a central component for organizing the natural nuclear architecture in malignancy cells. The focus of the present review is to provide an overview around the pharmacological functions of SUN2 in cancers. These findings suggest that SUN2 may serve as a encouraging therapeutic target and novel predictive marker in various types of malignancy. confirmed that SUN2 is required for attenuating excessive DNA damage in mouse embryonic fibroblasts (MEFs) from SUN1?/?SUN2?/? double knockout mice (16). Whether SUN2 participates in maintaining genomic stability in other types of malignancy needed further validation. Following recent improvements, this review presents recent information regarding the functions of SUN2 in the progression of malignancy and discusses the emerging signal pathways regulated by SUN2 in malignancy. 2.?Structure of SUN2 The LINC complex is a nuclear envelope protein complex that mainly consists of SUN and nesprin proteins, connecting nuclear lamina and cytoskeletal filaments (10), LINC complex characteristics of architecture framework helps to regulate the size and shape of the cell nucleus. Several SUN proteins have been identified in several organisms, including Sad1, UNC-84 and SUN1, and five human SUN proteins (17). Human SUN proteins can be grouped into two Isepamicin subfamilies based on their intracellular localization: SUN1 and SUN2 are integral membrane components of the inner nuclear membrane (INM) (18C20); SUN3 and the Rabbit Polyclonal to DHRS2 sperm-associated antigen 4 localize to endoplasmic reticulum and outer nuclear membrane (ONM) (21,22). SUN proteins are conserved among all eukaryotes and characterized by a C-terminal 200 amino acid SUN domain name (18,19,23C25). SUN proteins form a trimer through the SUN domain name and exhibits a perfect three-fold symmetry, resembling a cloverleaf (65 ? diameter) sitting on a short stem (30 ? of length) (26). As shown in Fig. 1, SUN2 extends into the perinuclear space by its C-terminal SUN domain name and interacts with nuclear lamina via its nucleoplasmic N-terminal domain name (11,27,28). Additionally, Isepamicin SUN2 connects with klarsicht/ANC-1/syne-1 homology (KASH) domain name, providing mechanical transduction between the cytoskeleton and nuclear interior, directly (19,22,28C30). Recent reports show that the SUN domain name is at the center of a nucleocytoplasmic bridge that is essential for nuclear motility in cells (31). These observations suggest that the structural characteristics of SUN2 are crucial for nuclear anchoring, migration, and positioning (19,22,29,30,32,33), centromere localization (34) and regulating the tethering of meiotic telomere (26). Thus, SUN2 may possess anti-cancer by regulating atypical nuclei structures in malignancy cells. Open in a separate window Physique 1. Schematic representation of SUN2 at the nuclear envelope. In Isepamicin the nuclear envelope, SUN2 exhibits a three-fold symmetry with its C-terminal extending into the perinuclear space and its nucleoplasmic N-terminal interacting with nuclear lamina. SUN2 connects with actin binding domain name through binding to the KASH domain name of Nesprin in cytoplasmic. The structure of SUN2 is usually functions as a bridge between the nuclear membrane and cytoplasm. SUN2, SAD1/UNC84 domain name protein-2; KASH, klarsicht/ANC-1/syne-1 homology; PNS, perinuclear space; INM, inner nuclear membrane; ONM, outer nuclear membrane. 3.?The role of SUN2 in different cancers Atypical teratoid/rhabdoid tumors (AT/RTs) AT/RT frequently occur in children. However, the pathogenesis of AT/RT remains to be uncovered. Several studies have indicated that this miR-221/222 gene cluster serves as an oncogenic miRNA in several types of human malignancy (35,36). Recently, miRNome and transcriptome characteristics in AT/RT were evaluated using small RNA sequencing and gene expression microarray analyses. Hsieh showed that miR-221/222-encoded Isepamicin miRNAs are abundantly expressed in AT/RT and substantially contribute to the malignancy of embryonal tumors (10). In AT/RT cells, overexpression of miR-221/222 prospects to faster cell growth, and this observation is supported by previous reports.
Reduced expression of lamin A/C was detected in colon cancer (37), small cell lung cancer (38), leukemias and lymphomas (39,40)