Alteration of membrane protein glycosylation in ovarian cancer

Among all women cancers, epithelial ovarian cancer is the fifth most common cause of cancer in women worldwide causing the highest mortality rate. An overview of the glycosylation landscape on cancer cell surface membrane glycoproteins is especially interesting as they have the potential to be used in clinical practice.

In this study, we analyzed the membrane glycosylation of non-cancerous ovarian surface epithelial and serous ovarian cancer cell lines. Glycan structures were characterized based on their molecular masses and tandem MS fragmentation patterns. Gene expression of specific glycosyltransferases in ovarian cancer cell lines is tested. Within a 2 day-treatment period with 5-Aza, we observed a significant increase of MGAT3 transcripts in non-cancerous cell lines as indicated by a relative MGAT3 expression of up to 324-fold and 83-fold. We found that MGAT3 expression may be epigenetically regulated by DNA hypomethylation, leading to the synthesis of the unique type N-glycans on the membrane proteins of ovarian cancer cells.

To summary, we identify specific N-glycan alterations on the cell surface membrane proteins of serous ovarian cancer cell lines that correlate with differential gene expression of the corresponding glycosyltransferase-encoded genes. Besides, we show that the primary glycosyltransferase alteration is epigenetically regulated via DNA methylation.

In addition to rheumatoid arthritis(RA), myeloproliferative neoplasm (MPN) is another disease which is closely related to regulation of JAK/STAT signaling pathway. Thus MPN and the related diseases often appear in my blog. In this post, I will continue to focus on this type of disease. The existing reports have demonstrated that the discovery of mutations activating JAK-STAT signaling in the majority of patients with myeloproliferative neoplasms (MPNs) leads to identification of tyrosine kinase activation as the common predominant mechanism causing MPN pathogenesis.

First of all, I will review the myeloproliferative neoplasms. Myeloproliferative neoplasms are a group of rare disorders of the bone marrow that cause an increase in the number of blood cells. The myeloproliferative neoplasms (MPNs) is found to usually exhibit terminal myeloid cell expansion in the peripheral blood, and mainly include primary myelofibrosis (PMF), essential thrombocythemia, chronic myeloid leukemia (CML), polycythemia vera, chronic neutrophilic leukemia, chronic eosinophilic leukemia, and mast cell disease.

About the treatment of MPNs, until now, there is still not a curative drug treatment for MPNs in spite of investigational drug therapies existing. At present, the common treatment mainly included chemotherapy, stem cell transplant, and the kinase inhibitors of related signaling pathways. Chemotherapy, a combination of anti-cancer drugs, is sometimes used to treat MPN, while chemotherapy tends to be relatively non-intensive. Stem cell transplant is an intensive form of treatment and the only potential cure for myelofibrosis. Since there are existing some side effects in some patients with MPNs after the treatment of the first two methods. Thus, recently, the kinase inhibitors, as the potential therapy, have been widely development. The most studied signaling pathway is the JAK/STAT pathways, and some inhibitors of JAKs even have been used in cilnical trials.

As I have mentioned many times, the activating JAK2V617F mutation have been observed in patients with MPNs, suggesting hyperactivation of JAK2 signaling appears to be necessary and sufficient for MPN development. Thus, it is suggested that an additional genetic change in the cells may occur before the JAK2 mutation and contribute to MPN development. Recent studies have shown that most mutations in

MPN patients besides JAK2, MPL, and LNK occur in genes whose function is known to be in the epigenetic regulation of gene transcription. For example, the transforming effects of activating mutations in JAK2 have been considered to result from constitutive activation of downstream mitogenic pathways such as the STAT family of transcription factors, MAPK, and AKT. Besides, JAK2 can also interacts with chromatin-modifying/reading proteins PRMT5 and impact histone arginine methylation[1].

In summary, there are some clinical and functional epigenetic alterations observed in the pathogenesis of MPNs, suggesting the changes may play the important roles on the development of MPNs. Thus further studies are needed to know the mechanism.

Numerologist Warda is hooked on OG-L002 fishing, collecting. And lastly her encouragement comes from socializing along with her companions.