Nischarin Is Differentially Expressed in Rat Brain and Regulates Neuronal Migration

Abstract

Nischarin is a protein known to inhibit breast cancer cell motility by regulating the signaling of the Rho GTPase family. However, little is known about its location and function in the nervous system. The aim of the present study was to investigate the regional and cellular expression and functions of Nischarin in the adult rodent brain. As assessed by real-time PCR, Western blot analysis and immunostaining, we found that Nischarin was widely distributed throughout the brain, with a higher expression in the cerebral cortex and hippocampus. Double-labeling showed that Nischarin was expressed in neurons and was mainly located in the perinuclear region and F-actin-rich protrusions. The expression pattern of Nischarin in the brain was thought to be closely associated with its function. This was verified by our findings from cell migration assays that Nischarin regulated neuronal migration. These results provide a preliminary survey of the distribution of Nischarin in different regions and cell types in the rat brain. This might help to elucidate its physiological roles, and to evaluate its potential clinical implications.

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

“…This hypothesis was also based on previous findings that linked Nischarin to decreasing the function of key cell attachment proteins, such as FAK (1,42). Also, it has been shown by other investigators that Nischarin regulates apoptosis and metastasis of breast cancer (43), loss of Nischarin promotes cell proliferation metastasis of ovarian cancer (42), and suppression of Nischarin promotes neuronal migration (44), suggesting that Nischarin has significant role in other cancers as well. We found that Nischarin-reduced cells had increased proliferation regardless of the substrate they were seeded on.…”

Breast Cancer Tumor Suppressors: A Special Emphasis on Novel Protein Nischarin

“…Nischarin is highly expressed on the leading edge of neurons (31). Silencing of Nischarin in both rat and mouse neurons has been found to increase neuronal migration (31).…”

“…Silencing of Nischarin in both rat and mouse neurons has been found to increase neuronal migration (31). Nischarin is expressed by mature neurons to prevent them from further migration (31). Neuronal migration is necessary in the embryonic period for normal brain formation (31).…”

“…Neuronal migration is necessary in the embryonic period for normal brain formation (31). Because Nischarin has higher expression in layers IV-V of the cortex, it is expressed by mature neurons that no longer need to migrate (31).…”

Expression of integrin-binding protein Nischarin in metastatic breast cancer

“…Nischarin mRNA expression levels have been reported to be significantly higher in the brain and kidney compared with those in the heart, liver, lung and skeletal muscle ( 19 ). Additionally, Nischarin expression was recently revealed to be widely distributed in rat brain tissue, particularly in the cerebral cortex and hippocampus, and is hypothesized to exhibit a significant role in neuronal migration ( 25 ).…”