Cancer statistics show significant diagnosis numbers amongst men and women worldwide, where breast cancer is by far the most frequently diagnosed cancer in women. Multiple mechanisms and molecules have been shown to occupy major roles in cancer progression and aggressivity. Recently, small non-coding RNA molecules, called micro-RNAs, have become the subject of interest in many molecular pathways in relation to breast cancer, amongst many other pathologies. MiRNAs are capable of regulating gene expression in a sequence-specific manner and regulate diverse expression patterns which are dependent on the cell's state and identity. Studies have brought forward specific miRNAs that have the innate ability to govern unique gene expression profiles regulating cancer cell aggressivity. This review will outline recent findings of characterized miRNAs in relation to their molecular targets leading to cancer malignancy and progression. More specifically, we will focus on miRNAs associated with breast cancer metastatic processes including epithelial to mesenchymal and mesenchymal to epithelial transitioning (EMT/MET transition), migration, invasion and angiogenesis.
S100 inflammatory proteins have been previously shown to modulate breast cancer processes. More specifically, genome-wide transcriptome studies associate S100A8 and S100A9 members to breast cancer progression and malignancy. Findings have shown that S100A8 and S100A9 can signal and regulate cancer cell behavior through both extracellular and intracellular-initiated cascades. However, functional studies exploring the effects of S100 proteins are often contradictory leaving ambiguity and a paucity of data relating to the specific function of S100A8 and S100A9 in breast cancer progression. In this study we sought to better define the functions of intracellular expressed S100A8 and S100A9 on key signaling and cellular processes driving breast cancer malignancy. We observed that extracellular treatments of the MCF7 breast cancer cell line with S100A8 and S100A9 proteins induces cell proliferation. In contrast, intracellular recombinant expression of S100A8 and S100A9 led to growth suppression. Furthermore our analysis revealed that intracellular-expressed S100A8 and S100A9 promote an epithelial-like phenotype through the induction of key markers, such as Ecadherin, integrin alpha-5 and Zona Occludens 1 (ZO-1). Concomitantly, S100A8 and S100A9 negatively regulate the activity of the promalignant Focal Adhesion Kinase-1 (FAK) signaling cascade leading to changes in cell adhesion and invasion properties. Our results uncover important differences in intracellular versus extracellular initiated S100A8 and S100A9 signaling cascades and their effects on mammary epithelial growth. Importantly, S100A8 and S100A9 appear to suppress breast cancer malignancy through an increase in mesenchymal to epithelial transitioning. Our findings shed insight into S100 protein involvement in breast cancer invasiveness and metastasis and clarify some of the controversies relating to these proteins in breast cancer processes.
The study of anticancer properties from natural products has regained popularity as natural molecules provide a high diversity of chemical structures with specific biological and medicinal activity. Based on a documented library of the most common medicinal plants used by the indigenous people of North America, we screened and isolated compounds with anti-breast cancer properties from Juniperus communis (common Juniper). Using bioassay-guided fractionation of a crude plant extract, we identified the diterpene isocupressic acid and the aryltetralin lignan deoxypodophyllotoxin (DPT) as potent inducers of caspase-dependent programmed cell death (apoptosis) in malignant MB231 breast cancer cells. Further elucidation revealed that DPT, in contrast to isocupressic acid, also concomitantly inhibited cell survival pathways mediated by the MAPK/ERK and NFκB signaling pathways within hours of treatment. Our findings emphasize the potential and importance of natural product screening for new chemical entities with novel anticancer activities. Natural products research complemented with the wealth of information available through the ethnobotanical and ethnopharmacological knowledge of the indigenous peoples of North America can provide new candidate entities with desirable bioactivities to develop new cancer therapies.
Mammaglobin 1 (MGB1), a member of the secretoglobin family, is expressed in mammary epithelial tissues and is overexpressed in most mammary carcinomas. Despite the extensive research correlating MGB1 expression profiles to breast cancer pathogenesis and disease outcome, the biological significance of MGB1 in cancer processes is still unclear. We have thus set out to conduct a functional evaluation of the molecular and cellular roles of MGB1 in breast cancer processes leading to disease progression. Using a series of breast cancer cell models with conditional MGB1 expression, we demonstrate that MGB1 promotes cancer cell malignant features. More specifically, loss of MGB1 expression resulted in a decrease of cell proliferation, soft agar spheroid formation, migration, and invasion capacities of breast cancer cells. Concomitantly, we also observed that MGB1 expression activates signaling pathways mediated by MAPK members (p38, JNK, and ERK), the focal adhesion kinase (FAK), matrix metalloproteinases (MMPs) and NFκB. Moreover, MGB1 regulates epithelial to mesenchymal (EMT) features and modulates Snail, Twist and ZEB1 expression levels. Interestingly, we also observed that expression of MGB1 confers breast cancer cell sensitivity to anticancer drug-induced apoptosis. Together, our results support a role for MGB1 in tumor malignancy in exchange for chemosensitivity. These findings provide one of the first descriptive overview of the molecular and cellular roles of MGB1 in breast cancer processes and may offer new insight to the development of therapeutic and prognostic strategies in breast cancer patients. © 2015 Wiley Periodicals, Inc.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.