Abstract
BackgroundSialic acids are widely distributed in animal tissues, and aberrantly expressed in a variety of cancer types. High expression of sialic acid contributes to tumor aggressiveness by promoting cell proliferation, migration, angiogenesis, and metastasis. Sialidases are responsible for removal of sialic acids from glycoproteins and glycolipids.MethodsN-glycomics of bladder cancer cells were detected by MALDI-TOF mass spectrometry. Sialic acid modification in bladder cancer tissue was determined by lectin blot. The down-regulation of NEU1 in bladder cancer cells was determined by high resolution liquid chromatography mass spectrometry (HR LC-MS). The effects of sialidase NEU1 expression on proliferation and apoptosis of human bladder cancer cells were examined by western blot, RT-PCR, confocal imaging and flow cytometry. Moreover, the function of sialic acids on fibronectin-integrin α5β1 interaction were assayed by immunoprecipitation and ELISA. The importance of NEU1 in tumor formation in vivo was performed using BALB/c-nu mice. Expression of NEU1 in primary human bladder cancer tissue samples was estimated using bladder cancer tissue microarray.Results(1) Downregulation of NEU1 was primarily responsible for aberrant expression of sialic acids in bladder cancer cells. (2) Decreased NEU1 expression was correlated with bladder cancer progression. (3) NEU1 overexpression enhanced apoptosis and reduced proliferation of bladder cancer cells. (4) NEU1 disrupted FN-integrin α5β1 interaction and deactivated the Akt signaling pathway. (5) NEU1 significantly suppressed in vivo tumor formation in BALB/c-nu mice.ConclusionsOur data showed that NEU1 inhibited cancer cell proliferation, induced apoptosis, and suppressed tumor formation both in vitro and in vivo, by disrupting interaction of FN and integrin β1 and inhibiting the Akt signaling pathway. Our observations indicate that NEU1 is an important modulator of the malignant properties of bladder cancer cells, and is a potential therapeutic target for prognosis and treatment of bladder cancer.9TmwM6TCi5jeGFE_4Mp_v7Video Graphical abstract
Highlights
Sialic acids are widely distributed in animal tissues, and aberrantly expressed in a variety of cancer types
Our data showed that NEU1 inhibited cancer cell proliferation, induced apoptosis, and suppressed tumor formation both in vitro and in vivo, by disrupting interaction of FN and integrin β1 and inhibiting the Akt signaling pathway
Our observations indicate that NEU1 is an important modulator of the malignant properties of bladder cancer cells, and is a potential therapeutic target for prognosis and treatment of bladder cancer
Summary
Sialic acids are widely distributed in animal tissues, and aberrantly expressed in a variety of cancer types. EMT is regulated by multiple signaling networks, including extracellular signalregulated protein kinases (ERKs), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/ Akt, Smads, RhoB, β-catenin and c-fos [12,13,14,15]. Other than these signaling factors, aberrant expression and high sensitivity of sialic acid as a tumor marker have been reported in a variety of cancerous conditions, and in many EMT models [16,17,18]. Sialic acid, whose production is catalyzed by polysialyltransferases ST8SIA2 and ST8SIA4, shows high aberrant expression on a variety of tumors [23]
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