Invasion of the Sensors

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Self-adaptive warning system for intelligently addressing circumferential intrusions of fiber Bragging grating. Fire-prevention and invasion-prevention synchronous early warning system and signal processing method thereof. An earth micro wave motion direction monitoring device and the tracking servo control system.

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Discoidin domain receptors: Microenvironment sensors that promote cellular migration and invasion. Itoh Y(1). Author information. Keywords:adhesion signaling, adhesion, cell adhesion, cell migration, Cell signaling, collagen, DDR, extracellular matrix, ECM, invasion, integrins, MMP.

Houston et al. Sections without incubation with primary antibody served as negative controls. The intensity of staining brown color was semi-quantitatively scored as follows: 1, weak; 2, medium; 3, strong; and 4, very strong. High expression of ASIC2 was defined as a combined score for the intensity and area of staining that was larger than 4.

The results were verified by two pathologists independently. All statistics were performed using SPSS P values less than 0. Survival analysis was assessed by using the Kaplan-Meier method, and survival rate was compared by log rank test. In this study, we first examined the effect of acidosis on the expression of ASICs. Acidosis-induced ASIC2 expression was further validated by immunofluorescence and western blotting Fig. The acidic environment leads to increased expression of ASIC2.

Results are representative of three independent experiments. Previous studies showed that acidosis promotes the invasion of CRC cells [ 5 ].

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S1B and 1C. S3A and 3B. Next, we measured the invasion capacity of CRC cells under acidosis. The invasion ability was measured by Transwell invasion assay. As shown in Fig. The average weight of xenografts significantly increased from 0. The average weight of xenografts was dramatically reduced from 0.

Each sample was tested in triplicates.

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Metastatic nodules in the liver were counted. Upon ASIC2 activation, calcium is elevated in the cytoplasm [ 20 ]. S3E and 3F. CsA also inhibited acidosis-induced invasion ability of SW cells Fig. Cell invasion ability was measured in the presence or absence of Cyclosporine A at the indicated concentration. Peaks were assigned to specific genes by proximity to the nearest transcription start site TSS. We also detected the expression of these genes after knock-down or overexpression of ASIC2.

S4B and 4C.

These results suggest that NFAT1 plays an important role in the invasion, migration, and metastasis of CRC by regulating gene transcription. ASIC2 was mainly expressed in the cell membrane and cytoplasm Fig.

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High expression of ASIC2 was detected in Positive nuclear NFAT1 was detected in ASIC2 expression was significantly increased in primary cancer. Tumor heterogeneity poses one of the main challenges for cancer therapy [ 22 ]. The tumor microenvironment remains one of the drivers causing heterogeneity [ 23 ]. As tumor cells tend to utilize aerobic glycolysis and present poor vasculature, the extracellular fluid in tumor tissues is often acidic, an event known as acidosis [ 24 ].

The acidic tumor microenvironment functions as a selection pressure on all cells in the tumor tissues. The tumor cells surviving in the hostile microenvironment exhibit stronger invasion and metastasis potential [ 25 ].

In , it was reported that reversing the acidic tumor microenvironment using bicarbonate inhibited metastasis of breast cancer cells in a mouse model [ 26 ]. Bicarbonate markedly enhanced the anticancer activity of transarterial chemoembolization for liver cancer in a clinical study [ 27 ]. The present study demonstrates that acidic stimulation leads to up-regulation of the acid sensing ion channel, ASIC2, which enhanced the invasion capacity of CRC cells.

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ASIC2 expression was increased in neurons of the cortex and hippocampus, which were susceptible to ischemic injury, but not in neurons with detectable DNA damage [ 29 ]. The present study demonstrates for the first time that ASIC2 overexpression enhances the progressive phenotype of CRC cells such as invasion and proliferation in vitro and in vivo, while ASIC2 knockdown had the opposite effect.

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Transcription factors of the NFAT family are important for various cellular processes, including T-cell activation, cardiac valve development, and osmotic stress response. Once in the nucleus, NFAT proteins form a complex with cell-type specific cofactors to control the transcription of target genes.

NFAT1 is constitutively expressed in T cells and functions as a critical player in T-cell activation [ 31 ]. CXCR1, also known as interleukin-8 receptor A, has been demonstrated to play important role in the proliferation, invasion, angiogenesis and metastasis of cancer cells [ 35 ]. As the regulatory mechanism by which acidosis induced the expression of ASIC2 is at present largely unknown, future work should be done to demonstrate it.

InvestigAge

The results revealed that high expression of ASIC2 correlated with recurrence, invasion depth, and distant metastasis. It should be note that the present study is limited to the acute effect of acidosis on the ASICs expression. Our future work will focus on the chronic effect of acidosis on ASICs expression and the underlying mechanism. Cancer Res. Evaluating tumor metastatic potential by imaging intratumoral acidosis via pH-activatable near-infrared fluorescent probe.

Int J Cancer. The genomic analysis of lactic acidosis and acidosis response in human cancers. PLoS Genet. Acid treatment of melanoma cells selects for invasive phenotypes. Clin Exp Metastasis. Acidity generated by the tumor microenvironment drives local invasion. Hypoxia and acidosis independently up-regulate vascular endothelial growth factor transcription in brain tumors in vivo. Acid-sensing ion channels: advances, questions and therapeutic opportunities.

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Trends Neurosci. Acid-sensing ion channels contribute to the effect of acidosis on the function of dendritic cells. J Immunol. Identification of acid-sensing ion channels in bone. Biochem Biophys Res Commun.

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ASIC proteins regulate smooth muscle cell migration. Microvasc Res. Blockade of acid-sensing ion channels protects articular chondrocytes from acid-induced apoptotic injury. Inflamm Res. Regulation of breast tumorigenesis through acid sensors. J Physiol Biochem. Nuclear factor of activated T cells in cancer development and treatment. Cancer Lett. Transcription factor NFAT1 activates the mdm2 oncogene independent of p J Biol Chem. Expression and unique functions of four nuclear factor of activated T cells isoforms in non-small cell lung cancer.

Chin J Cancer. NFAT1 is highly expressed in, and regulates the invasion of, glioblastoma multiforme cells. PLoS One. Hyperactivation of the mammalian degenerin MDEG promotes caspase-8 activation and apoptosis. Cell Death Dis. Nuclear factor one transcription factors as epigenetic regulators in cancer. Cancer-associated fibroblasts promote irradiated cancer cell recovery through autophagy. Damaghi M, Gillies R: Phenotypic changes of acid adapted cancer cells push them toward aggressiveness in their evolution in the tumor microenvironment.