Abstract
Background: The carbohydrate antigen Sda and its biosynthetic enzyme B4GALNT2 are highly expressed in normal colonic mucosa but are down-regulated to a variable degree in colon cancer tissues. Here, we investigated the clinical and biological importance of B4GALNT2 in colon cancer. Methods: Correlations of B4GALNT2 mRNA with clinical data were obtained from The Cancer Genome Atlas (TCGA) database; the phenotypic and transcriptomic changes induced by B4GALNT2 were studied in LS174T cells transfected with B4GALNT2 cDNA. Results: TCGA data indicate that patients with high B4GALNT2 expression in cancer tissues display longer survival than non-expressers. In LS174T cells, expression of B4GALNT2 did not affect the ability to heal a scratch wound or to form colonies in standard growth conditions but markedly reduced the growth in soft agar, the tridimensional (3D) growth as spheroids, and the number of cancer stem cells, indicating a specific effect of B4GALNT2 on the growth in poor adherence and stemness. On the transcriptome, B4GALNT2 induced the down-regulation of the stemness-associated gene SOX2 and modulated gene expression towards an attenuation of the cancer phenotype. Conclusions: The level of B4GALNT2 can be proposed as a marker to identify higher- and lower-risk colorectal cancer patients.
Highlights
Colorectal cancer (CRC) remains a worldwide leading cause of cancer deaths, notwithstanding the improved efficacy of the available therapies
We show for the first time that in a large cohort of colon cancer samples, the mRNA
We observed that all patients surviving beyond three years displayed a high level of B4GALNT2 mRNA, indicating a strong relationship between high B4GALNT2 and lower malignancy
Summary
Colorectal cancer (CRC) remains a worldwide leading cause of cancer deaths, notwithstanding the improved efficacy of the available therapies. The last step of the Sda antigen biosynthesis is mediated by the enzyme β1,4N-acetylgalactosaminyltransferase 2 (B4GALNT2) [3], the product of the B4GALNT2 gene [4,5,6]. Transcription of the B4GALNT2 gene generates at least two different transcripts that only differ in the first exon These two transcripts contain a translational start site, from which two different transmembrane polypeptides originate: one, referred to as “long form”, contains an unusually. The carbohydrate antigen Sda and its biosynthetic enzyme B4GALNT2 are highly expressed in normal colonic mucosa but are down-regulated to a variable degree in colon cancer tissues. Methods: Correlations of B4GALNT2 mRNA with clinical data were obtained from The. Cancer Genome Atlas (TCGA) database; the phenotypic and transcriptomic changes induced by. Conclusions: The level of B4GALNT2 can be proposed as a marker to identify higher- and lower-risk colorectal cancer patients
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