GPAA1 facilitates the expression of cancer-related GPI-anchored proteins and supplies a more robust platform-the lipid raft-to promote EGFR-ERBB2 dimerization, which further contributes to tumour growth and metastasis and to cancer progression.
In this review, I summarize the current understanding of PG terminal synthases, with a focus on microsomal PGE synthase-1 (mPGES-1) and PGI synthase (PGIS). mPGES-1 and PGIS cooperatively exacerbate inflammatory reactions but have opposing effects on carcinogenesis. mPGES-1 and PGIS are expected to be attractive alternatives to COX as therapeutic targets for several diseases, including inflammatory diseases and cancer.
The top three ranked differential pathways were CREB phosphorylation, attachment of GPI anchor to urokinase plasminogen activator receptor (uPAR) and loss of function of SMAD2/3 in cancer.
Thus formulation of TA-CIN with GPI-0100 and intra-tumoral delivery after cisplatin treatment elicits potent therapeutic responses in a murine model of HPV16+ cancer.
The results show that the expression of Dicer1 (P=0.001), Drosha (P=0.01), DGCR8 (P=0.02), and Ago2 (P=0.002) mRNAs in cancer tissues of patients with PGI-DLBCL was significantly lower than those in normal tissues of healthy controls.
By regulating ER calcium release, AMF/PGI interaction with gp78/AMFR therefore protects against ER stress identifying novel roles for these cancer-associated proteins in promoting tumor cell survival.
Recent studies have revealed that silencing of AMF/PGI resulted in mesenchymal-to-epithelial transition (MET) of human lung fibrosarcoma cells and breast cancer cells with reduced malignancy.
These results suggest for the first time that PGI/AMF is a key gene to both EMT in the initiating step of cancer metastasis and MET in the later stage of metastasis during breast cancer progression.