sp²‐Iminosugar α‐glucosidase inhibitor 1‐C‐octyl‐2‐oxa‐3‐oxocastanospermine specifically affected breast cancer cell migration through Stim1, β1‐integrin, and FAK signaling pathways

Abstract

Aberrant glycosylation changes on many glycoproteins are often related to cancer progression and metastasis. sp -Iminosugar-type castanospermine analogues, inhibitors of α-glucosidases, have been reported to exhibit antitumor activity. However, their effects on cell migration and the underlying molecular mechanism are not fully understood. Here, we investigated the effect of the pseudo-C-octyl glycoside 2-oxa-3-oxocastanospermine derivatives (CO-OCS) on breast cancer cells (MCF-7 and MDA-MB-231 cells), and MCF-10A mammary normal cell lines. We showed that CO-OCS treatment results in the drastic decrease of breast cancer cell migration without affecting cell proliferation. Furthermore, CO-OCS significantly reduced both the expression of β1-integrin, which is a crucial interacting partner of Focal Adhesion Kinase (FAK), and the phosphorylation rates of FAK and ERK1/2. CO-OCS also drastically reduced Ca entry through Store Operated Channels (SOC). Orai1 and Stim1, two N-glycosylated proteins, are involved in Store-Operated Calcium Entry (SOCE), and are essential for breast tumor cell migration. Our results showed that CO-OCS decreased the expression, at the protein level, of Stim1 without affecting that of Orai1. Moreover, cell migration and SOCE were attenuated by CO-OCS as well as when Stim1 was silenced. In contrast, in MCF-10A cells, CO-OCS slightly reduced cell migration, but was without effect on gene expression of Stim1, Orai1, β1-integrin, or FAK and ERK1/2 activation. Our results provide strong evidence for a significant effect of CO-OCS on breast cancer cell migration and support that this effect was associated with β1-integrin, Stim1, and FAK signaling pathways.

The sp 2 -iminosugar glycolipid 1-dodecylsulfonyl-5 N ,6 O -oxomethylidenenojirimycin (DSO 2 -ONJ) as selective anti-inflammatory agent by modulation of hemeoxygenase-1 in Bv.2 microglial cells and retinal explants

“…It is important to note that HO-1 and IL-10 can perpetuate their anti-inflammatory effects in a reciprocal manner [49]. Moreover, both HO-1-induced IL-10 production and IL-10induced HO-1 activation are dependent on p38α MAPK activation [50][51][52][53]. In this regard our results strongly suggest that DSO 2 -ONJ selectively up-regulates the synthesis of the anti-inflammatory cytokine IL-10 in a manner likely dependent on HO-1 due to both the canonical and non-canonical p38α MAPK activation [58].…”

Multifunctional Silica-Based Nanoparticles with Controlled Release of Organotin Metallodrug for Targeted Theranosis of Breast Cancer

“…Within the receptor that meet these criteria, the folate receptor alpha (a glycosylphosphatidylinositol (GPI) anchored cell surface glycoprotein that is able to bind free folate with high affinity) represents a good candidate being overexpressed by many cancer tissues (ovarian, epithelial, cervical, lung, kidney, brain, colorectal, and breast tumors) [10][11][12]. More specifically, the folate receptor alpha is overexpressed in many TNBCs cells, including the MDA-MB-231 cell line [13][14][15][16].…”

Adenylyl Cyclase Type 8 Overexpression Impairs Phosphorylation-Dependent Orai1 Inactivation and Promotes Migration in MDA-MB-231 Breast Cancer Cells

“…TNBC cells overexpress Orai1, which is responsible for the activation of store-operated Ca 2+ entry (SOCE) [6]. Orai1 is a well-characterized regulator of the proliferation and migration of many TNBC cells, including the MDA-MB-231 cell line [7][8][9].…”