Downregulation of glypican-4 facilitates breast cancer progression by inducing cell migration and proliferation (original) (raw)

Glypican-4 (GPC-4) is a heparan sulphate glycoprotein, associated with cell membrane via a Glycosyl phosphatidyl (GPI)-anchor. It is involved in cell migration, cell growth, differentiation and morpho-genesis as well as chemoresistance and cancer stem cell maintenance in pancreatic cancer. However, its role in breast cancer remains unclear. To elucidate the role of GPC-4 in breast cancer, we analyzed GPC-4 expression in breast cancer patients and breast cancer cell lines. Our results demonstrated that GPC-4 expression was downregulated in metastatic tumors as compared to non-metastatic tumors. Further, GPC4's downregulation was confirmed in breast cancer metastatic cells (MDA-MBA-231 and MDA-MB-LM2) compared to non-metastatic cells (T47-D and MCF-7) with quantitative PCR and western blot. Knock-down of GPC-4 in non-metastatic cells significantly increased cell-migration and invasion. Similarly , over-expressing GPC-4 in metastatic cells decreased cell-migration/invasion and cell proliferation. Additionally, GPC-4 overexpression decreased in-vivo tumorigenicity in nude mice. Therefore, this research for the first time, has established the role of glypican-4 as a tumor-suppressor in breast cancer by decreasing migration and proliferation, revealing it as a possible therapy for breast cancer.