Nischarin regulates focal adhesion and Invadopodia formation in breast cancer cells

Abstract

BackgroundDuring metastasis, tumor cells move through the tracks of extracellular matrix (ECM). Focal adhesions (FAs) are the protein complexes that link the cell cytoskeleton to the ECM and their presence is necessary for cell attachment. The tumor suppressor Nischarin interacts with a number of signaling proteins such as Integrin α5, PAK1, LIMK1, LKB1, and Rac1 to prevent cancer cell migration. Although previous findings have shown that Nischarin exerts this migratory inhibition by interacting with other proteins, the effects of these interactions on the entire FA machinery are unknown.MethodsRT-PCR, Western Blotting, invadopodia assays, and immunofluorescence were used to examine FA gene expression and determine whether Nischarin affects cell attachment, as well as the proteins that regulate it.ResultsOur data show that Nischarin prevents cell migration and invasion by altering the expression of key focal adhesion proteins. Furthermore, we have found that Nischarin-expressing cells have reduced ability to attach the ECM, which in turn leads to a decrease in invadopodia-mediated matrix degradation.ConclusionsThese experiments demonstrate an important role of Nischarin in regulating cell attachment, which adds to our understanding of the early events of the metastatic process in breast cancer.Electronic supplementary materialThe online version of this article (10.1186/s12943-018-0764-6) contains supplementary material, which is available to authorized users.

GNG5 is a novel oncogene associated with poor prognosis in glioma patients

“…Similar interactions have been described previously; for example, the ECM-receptor interaction is involved in the proliferation and invasion of cancer cells [35,36], and focal adhesion is involved in the metastasis and invasion of cancer cells [37]. Additionally, the toll-like receptor promotes the immune evasion of glioma by down-regulating the MHC II molecules in microglia [38], and cell adhesion molecules and the nod-like receptor play a signi cant role in the proliferation, invasion, and metastasis of glioma cells [39][40][41][42].…”

GNG5 is a Novel Oncogene Associated with Poor Prognosis in Glioma Patients

“…6). Similar interactions have been described previously; for example, the ECM-receptor interaction is involved in the proliferation and invasion of cancer cells [35,36], and focal adhesion is involved in the metastasis and invasion of cancer cells [37]. Additionally, the toll-like receptor promotes the immune evasion of glioma by down-regulating the MHC II molecules in microglia [38], and cell adhesion molecules and the nod-like receptor play a signi cant role in the proliferation, invasion, and metastasis of glioma cells [39][40][41][42].…”

Exosomes from Nischarin-Expressing Cells Reduce Breast Cancer Cell Motility and Tumor Growth

“…Previous reports show that culturing noncancerous cells in conditioned media from cancer cells promotes proliferation and migration of noncancerous cells (26,27). We previously determined that incubating noncancerous MCF10A cells with media from 231 cells promotes cell migration (28). Incubating the cells with media from 231 Nisch cells promotes a moderate amount of cell migration, but significantly less than media from 231 cells (28).…”

“…We previously determined that incubating noncancerous MCF10A cells with media from 231 cells promotes cell migration (28). Incubating the cells with media from 231 Nisch cells promotes a moderate amount of cell migration, but significantly less than media from 231 cells (28). These results suggest that Nischarin is regulating the cancer cell secretome.…”