Clinical implications of AGBL2 expression and its inhibitor latexin in breast cancer

Abstract

BackgroundWe investigated the expression status of AGBL2 and its inhibitor latexin in breast cancer stem cells and its clinical implications in order to lay a foundation for managing breast cancer.MethodsCD44+/CD24- tumor cells (CSC) from clinical specimens were sorted using flow cytometry. AGBL2 expression status was detected in CSC and 126 breast cancer specimens by western blot and immunohistochemistry staining. The relationship between the AGBL2 protein and clinicopathological parameters and prognosis was subsequently determined.ResultAs a result, CSC are more likely to generate new tumors in mice and cell microspheres that are deficient in non-obese diabetic/severe combined immunodeficiency mice (NOD/SCID) compared to the control group. The AGBL2 protein was expressed higher in CSC induced to epithelial to mesenchymal transition (EMT) when compared to the control cells, and was found to be related to CSC chemotherapy resistance. After Spearman regression correlation analysis, AGBL2 was observed to be related to clinical stage, histological stage, and lymph node metastasis. In the Cox regression test, the AGBL2 protein was detected as an independent prognostic factor. Through immunoprecipitation, AGBL2 and latexin could form immune complexes.ConclusionsThese results demonstrate that AGBL2 is a latexin-interacting protein that regulates the tubulin tyrosination cycle and is a potential target for intervention.

Shared genetic architecture between metabolic traits and Alzheimer’s disease: a large-scale genome-wide cross-trait analysis

“…After pruning, we found 4 loci that were associated with both AD and fasting glucose at the genome wide significance level in the cross-trait meta-analysis ( Table 2). The first locus (index SNP: rs10501320, P meta =2.80×10 −16 ), was in close proximity to genes MADD, ACP2 and AGBL2, which was found to play roles in insulin sensitivity (Wagner et al 2011), lysosome and cerebellar function (van de Bunt et al 2015) and immune complexes (Zhang et al 2014). The second loci (index SNP: rs12805422, P meta =1.57×10 −13 ) was mapped to the genes C11orf94 and CRY2 which encode for a flavin adenine dinucleotide-binding protein involved in regulating the circadian clock.…”

Latexin exhibits tumor-suppressor potential in pancreatic ductal adenocarcinoma

“…Furthermore, they showed that Lxn has a tumor-suppressive role and that it negatively regulates the expression of tumor-sustaining stem cell factors ( 19 ). Recently, Lxn has been demonstrated to be a tumor-suppressor gene in gastric cancer ( 38 ), hepatocellular carcinoma ( 39 ), melanoma ( 19 ), leukemia ( 40 ), prostate ( 41 ) and breast cancer ( 42 ). Our previous study revealed that Lxn induced the apoptosis and inhibited the proliferation of CD133 + MIA PaCa-2 pancreatic cancer cells ( 20 ).…”

Bone Microenvironment Changes in Latexin Expression Promote Chemoresistance

“…It has been previously demonstrated that hypermethylation of CpG islands was found to be highly correlated with the transcriptional silencing of LXN gene (14–16). Furthermore, consistent with its role as tumor suppressor, the LXN gene has been shown to be silenced by methylation in several different cancers (14–16,38–40). Our findings that demethylation treatment of the PCa cells restored LXN expression are consistent with these previous reports suggesting that methylation of the LXN gene contributes to its downregulation in the chemoresistant PCa cells.…”

“…LXN has homology to two other proteins/genes, tazarotene-induced gene 1 (TIG1) and cystatin C, both of which have been reported to be tumor suppressors (36,37). LXN expression has been suggested to be a tumor suppressor itself as it has been shown to inhibit tumor cell growth in gastric cancer (14), leukemia (15), melanoma (16), PCa (38), hepatocellular carcinoma (39) and breast cancer (40). In addition to being a potential tumor suppressor, LXN negatively regulates hematopoietic stem cell self-renewal in mice, resulting in an inverse relationship between LXN expression and HSC population size (17,18,41).…”