The Role of the Adapter Protein Anks1a in the Regulation of Breast Cancer Cell Motility.

Epithelial-mesenchymal transition (EMT) is a critical step in tumor progression that leads to the acquisition by cancer cells the capacity for migration using the mesenchymal motility mode regulated by the Rac→WAVE→Arp2/3 signaling pathway. Earlier it was shown that proteins interacting with Rac can regulate mesenchymal migration and thus determine the metastatic potential of the cells. The search for new regulators of cell migration is an important theoretical and practical task. The adaptor protein Anks1a is one of the proteins interacting with Rac, whose expression is altered in many types of tumors. The aim of this study was to find whether Anks1a affects the migration of cancer cells and to identify the mechanism underlying this effect. It was suggested that Anks1a can influence cancer cell migration either as a Rac1 effector or by activating human epidermal growth factor receptor 2 (HER2) exchange. We investigated how upregulation and inhibition of Anks1a expression affected migration of breast cancer cells with different HER2 status. Anks1a was shown to interact with the activated form of Rac1. In the MDA-MB-231 cells (triple negative cancer), which lack HER2, Anks1a accumulated at the active cell edge, which is characterized by enrichment with active Rac1, whereas no such accumulation was observed in the HER2-overexpressing SK-BR-3 cells. Downregulation of the ANKS1a expression with esiRNA had almost no effect on the cancer cell motility, except a slight increase in the average migration rate of MDA-MB-231 cells. Among three cell lines tested, overexpression of Anks1a increased the migration rate of HER2-overexpressng SK-BR-3 cells only. We showed that Anks1a is an effector of activated Rac1, but its influence on the cell migration in this capacity was minimal, at least in the studied breast cancer cells. Anks1a affected the motility of breast cancer cells due to its involvement in the EGF receptor exchange.

Phase Coupling Between Baroreflex Oscillations of Blood Pressure and Heart Rate Changes in 21-Day Dry Immersion.

INTRODUCTION: Dry immersion (DI) is a ground-based experimental model which reproduces the effects of microgravity on the cardiovascular system and, therefore, can be used to study the mechanisms of post-flight orthostatic intolerance in cosmonauts. However, the effects of long-duration DI on cardiovascular system have not been studied yet. The aim of this work was to study the effects of 21-day DI on systemic hemodynamics and its baroreflex control at rest and during head-up tilt test (HUTT). METHODS: Ten healthy young men were exposed to DI for 21 days. The day before, on the 7th, 14th, and 19th day of DI, as well as on the 1st and 5th days of recovery they were subjected to HUTT: 15 min in supine position and then 15 min of orthostasis (60°). ECG, arterial pressure, stroke volume and respiration rate were continuously recorded during the test. Phase synchronization index (PSI) of beat-to-beat mean arterial pressure (MAP) and heart rate (HR) in the frequency band of baroreflex waves (∼0.1 Hz) was used as a quantitative measure of baroreflex activity. RESULTS: During DI, strong tachycardia and the reduction of stroke volume were observed both in supine position and during HUTT, these indicators did not recover on post-immersion day 5. In contrast, systolic arterial pressure and MAP decreased during HUTT on 14th day of DI, but then restored to pre-immersion values. Before DI and on day 5 of recovery, a transition from supine position to orthostasis was accompanied by an increase in PSI at the baroreflex frequency. However, PSI did not change in HUTT performed during DI and on post-immersion day 1. The amplitude of MAP oscillations at this frequency were increased by HUTT at all time points, while an increase of respective HR oscillations was absent during DI. CONCLUSION: 21-day DI drastically changed the hemodynamic response to HUTT, while its effect on blood pressure was reduced between days 14 and 19, which speaks in favor of the adaptation to the conditions of DI. The lack of increase in phase synchronization of baroreflex MAP and HR oscillations during HUTT indicates disorders of baroreflex cardiac control during DI.