Fibrinogen is an extracellular matrix protein composed of three polypeptide chains with fibrinogen alpha (FGA), beta (FGB) and gamma (FGG). While fibrinogen and its related fragments are involved in tumor angiogenesis and metastasis, their functional roles are incompatible. A recent genome-scale screening reveals that loss of FGA affects the acceleration of tumor growth and metastasis of lung cancer, but the mechanism remains elusive. We used CRISPR/Cas9 genome editing to knockout (KO) FGA in human lung adenocarcinoma (LUAD) cell lines A549 and H1299. By colony formation, transwell migration and matrix invasion assays, FGA KO increased cell proliferation, migration, and invasion but decreased the expressions of epithelial-mesenchymal transition marker E-cadherin and cytokeratin 5/8 in A549 and H1299 cells. However, administration of FGA inhibited cell proliferation and migration but induced apoptosis in A549 cells. Of note, FGA KO cells indirectly co-cultured by transwells with FGA wild-type cells increased FGA in the culture medium, leading to decreased migration of FGA KO cells. Furthermore, our functional analysis identified a direct interaction of FGA with integrin α5 as well as FGA-integrin signaling that regulated the AKT-mTOR signaling pathway in A549 cells. In addition, we validated that FGA KO increased tumor growth and metastasis through activation of AKT signaling in an A549 xenograft model. Implications These findings demonstrate that that loss of FGA facilities tumor growth and metastasis through integrin-AKT signaling pathway in lung cancer. Copyright ©2020, American Association for Cancer Research.Malignant cancer cells can invade extracellular matrix (ECM) through the formation of F-actin-rich subcellular structures termed invadopodia. ECM degradation at invadopodia is mediated by matrix metalloproteinases (MMPs), and recent findings indicate that membrane-anchored membrane type 1-matrix metalloproteinase (MT1-MMP) has a primary role in this process. Maintenance of an invasive phenotype is dependent on internalization of MT1-MMP from the plasma membrane and its recycling to sites of ECM remodeling. Internalization of MT1-MMP is dependent on its phosphorylation, and here we examine the role of β1 integrin-mediated signaling in this process. Activation of β1 integrin using the antibody P4G11 induced phosphorylation and internalization of MT1-MMP and resulted in increased cellular invasiveness and invadopodium formation in vitro We also observed phosphorylation of Src and epidermal growth factor receptor (EGFR) and an increase in their association in response to β1 integrin activation, and determined that Src and EGFR promote phosphorylation of MT1-MMP on Thr567 These results suggest that MT1-MMP phosphorylation is regulated by a β1 integrin-Src-EGFR signaling pathway that promotes recycling of MT1-MMP to sites of invadopodia formation during cancer cell invasion. © 2020. Published by The Company of Biologists Ltd.Muscle is highly organized across multiple length scales. Consequently, small changes in the arrangement of myofilaments can influence macroscopic mechanical function. Two leg muscles of a cockroach, have identical innervation, mass, twitch responses, length-tension curves, and force-velocity relationships. However, during running, one muscle is dissipative (a "brake"), while the other dissipates and produces significant positive mechanical work (bifunctional). Using time resolved x-ray diffraction in intact, contracting muscle, we simultaneously measured the myofilament lattice spacing, packing structure, and macroscopic force production of these muscle to test if structural differences in the myofilament lattice might correspond to the muscles' different mechanical functions. While the packing patterns are the same, one muscle has 1 nm smaller lattice spacing at rest. Under isometric activation, the difference in lattice spacing disappeared consistent with the two muscles' identical steady state behavior. During periodic contractions, one muscle undergoes a 1 nm greater change in lattice spacing, which correlates with force. This is the first identified structural feature in the myofilament lattice of these two muscles that shares their whole muscle dynamic differences and quais-static similarities. © 2020. Published by The Company of Biologists Ltd.Cobitis species exist in diploid populations, but mostly they occur in diploid-polyploid (d-p) ones. They are considered an important model organism to study biology and physiology of natural hybrid and polyploid vertebrates. Indeed, polyploidization causes a huge stress for the cell physiology and alter spermatogenesis in polyploid fish. Selleck Y-27632 The most extensively studied modes of germ cell death during spermatogenesis in vertebrates is apoptosis. The aim of the study was to examine the caspase-3 immunoexpression in the testes of Cobitis taenia from diploid population as well as C. taenia and sterile tetraploid Cobitis from d-p population before, during and after spawning. The obtained results suggest a different performance of apoptosis in testes of C. taenia from both studied populations and seems to be conditioned by their role as the only sperm donors in d-p populations. Moreover, apoptosis was active cell death process in the testes of tetraploid Cobitis. © 2020. Published by The Company of Biologists Ltd.This study evaluated the effect of exposure to either a chronic variable stress (CVS) protocol or social isolation, as well as to treadmill exercise training, in the habituation of the cardiovascular responses upon repeated exposure to restraint stress in rats. The habituation of the corticosterone response to repeated restraint stress was also evaluated. For this, animals were subjected to either acute or 10 daily sessions of 60 min of restraint stress. CVS and social isolation protocols lasted 10 consecutive days, whereas treadmill training was performed 1h/day, 5 days/week for 8 weeks. We observed that serum corticosterone increase was decreased during both the stress and the recovery period of the 10th session of restraint. Habituation of the cardiovascular responses was identified in terms of a faster return of heart rate to baseline values during the recovery period of the 10th session of restraint. The increase in blood pressure and the decrease in tail skin temperature were similar at the first and 10th session of restraint.