Up-regulated expression of type II very low density lipoprotein receptor correlates with cancer metastasis and has a potential link to β-catenin in different cancers

Abstract

BackgroundVery low density lipoprotein receptor (VLDLR) has been considered as a multiple function receptor due to binding numerous ligands, causing endocytosis and regulating cellular signaling. Our group previously reported that enhanced activity of type II VLDLR (VLDLR II), one subtype of VLDLR, promotes adenocarcinoma SGC7901 cells proliferation and migration. The aim of this study is to explore the expression levels of VLDLR II in human gastric, breast and lung cancer tissues, and to investigate its relationship with clinical characteristics and β-catenin expression status.MethodsVLDLR II expression was examined using immunohistochemistry (IHC) and Western blot in tumor tissues from 213 gastric, breast and lung cancer patients, tumor adjacent noncancerous tissues by same methods. Correlations between VLDLR II and clinical features, as well as β-catenin expression status were evaluated by statistical analysis.ResultsThe immunohistochemical staining of VLDLR II showed statistical difference between tumor tissues and tumor adjacent noncancerous tissues in gastric, breast and lung cancers (P = 0.034, 0.018 and 0.043, respectively). Moreover, using Western, we found higher VLDLR II expression levels were associated with lymph node and distant metastasis in gastric and breast cancer (P < 0.05). Furthermore, highly significant positive correlations were found between VLDLR II and β-catenin in gastric cancer (r = 0.689; P < 0.001)breast cancer (r = 0.594; P < 0.001).ConclusionsAccording to the results of the current study, high VLDLR II expression is correlated with lymph node and distant metastasis in gastric and breast cancer patients, the data suggest that VLDLR II may be a clinical marker in cancers, and has a potential link with β-catenin signaling pathway. This is the first to reveal the closer relationship of VLDLR II with clinical information.

Lipoprotein internalisation induced by oncogenic AMPK activation is essential to maintain glioblastoma cell growth

“…Here we show that AMPK is also critical to maintain cell growth by increasing the expression of lipoprotein receptors and therefore stimulating lipoprotein internalisation. In agreement with our data, previous reports have shown that VLDLr, LDLr and ABCG1 are necessary to maintain viability in several human tumours [1,12,31], and it has been widely shown that the LDL receptor family participates in tumourigenesis [20,30]. Furthermore, it has been reported by others that certain AMPK-activating stimuli induce VLDLr expression and increase ABCG1 mRNA and protein levels [19,34].…”

Nuciferine, extracted from Nelumbo nucifera Gaertn, inhibits tumor-promoting effect of nicotine involving Wnt/β-catenin signaling in non-small cell lung cancer

“…To gauge both stain intensity and uniformity simultaneously, the average values for intensity for each tissue were multiplied by the average values for percentage area stained in each tissue to derive a composite histoscore (i.e., histoscore¼area  intensity), the grading system for histoscore was presented as described previously (He et al, 2010).…”

“…Protein quantification was performed using the Bradford method and all the samples were prepared for western blot. Western blot assay was done as described previously (He et al, 2010).…”

Phenotype-driven transitions in regulatory network structure

“…We note that many of the developmental genes in these modules are associated with breast cancer. Among genes annotated with "nervous system development," the fibroblast growth factor receptor (FGFR) is often amplified or dysregulated in breast cancer, the HES5 locus is repositioned in invasive breast cancer, and VLDLR is often upregulated in metastatic breast cancer (82)(83)(84)(85). The blood vessel development category included genes such as GATA6, a known oncogene that may drive EMT in the breast; TBX3, which appears to repress the tumor suppressor p14ARF and drive metastatic breast cancer; PRRX2, which increases invasiveness in breast tumors; and RASA1, whose expression is associated with poor prognosis in breast cancer (86)(87)(88)(89).…”