Downregulation of glypican-4 facilitates breast cancer progression by inducing cell migration and proliferation

Abstract

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 morphogenesis 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.