Expression of FAP-1 Correlates with Glioblastoma Proliferation, Migration and Treatment Resistance

2020 ◽  
Author(s):  
Bo Li ◽  
Yang Liu ◽  
Shaya Mahati ◽  
Hu Qin ◽  
Aisha Maimaitili ◽  
...  
Keyword(s):  
Tyrosine Phosphatase ◽  
Treatment Resistance ◽  
Residual Tumor ◽  
Large Protein ◽  
Average Survival Time ◽  
Resistance To Therapy ◽  
Average Survival ◽  
And Migration ◽  
Severe Type

Abstract Background: Glioblastoma (GBM) is the most severe type of brain cancer, with an extremely high mortality rate and the average survival time less than 15 months. Almost in all GBM cases, the residual tumor cells continue to divide uncontrollably, leading to tumor re-establishment, i.e., tumor recurrence, and ultimately death. Therefore, there is an urgent need to identify critical mediators of GBM progression and resistance to therapy. Fas-associated Phosphatase-1 (FAP-1, also known as PTPN13 or PTPL1) is a member of a large protein tyrosine phosphatase family. It has been shown that FAP-1 expression is downregulated in many types of cancers, which leads to unabated signaling and tumor progression and metastasis. The aim of this study is to evaluate the role of FAP-1 in GBM progression and resistance to therapy.Methods: Cell viability assays, radiotherapy and temozolomide response assays, and Western blot were used to analysis of FAP-1 in GBM based on Oncomine.Results: Our results showed that knockdown of FAP-1 enhanced viability and migration of GBM cell lines, and importantly, increased GBM cell resistance to radiotherapy and temozolomide. Conclusions: FAP-1 is important for GBM cells, and may account for GBM resistance to therapy.

scholarly journals Paradoxical role of high mobility group box 1 in glioma: a suppressor or a promoter?

2017 ◽  
Author(s):  
Richard A. Seidu ◽  
Min Wu ◽  
Zhaoliang Su ◽  
Huaxi Xu
Keyword(s):  
Molecular Mechanisms ◽  
High Mobility ◽  
Treatment Resistance ◽  
High Mobility Group ◽  
Tissue Invasion ◽  
Self Sufficiency ◽  
Glycation End Products ◽  
And Migration ◽  
Proliferation And Migration

Gliomas represent 60% of primary intracranial brain tumors and 80% of all malignant types, with highest morbidity and mortality worldwide. Although glioma has been extensively studied, the molecular mechanisms underlying its pathology remain poorly understood. Clarification of the molecular mechanisms involved in their development and/or treatment resistance is highly required. High mobility group box 1 protein (HMGB1) is a nuclear protein that can also act as an extracellular trigger of inflammation, proliferation and migration, through receptor for advanced glycation end products and toll like receptors in a number of cancers including gliomas. It is known that excessive release of HMGB1 in cancer leads to unlimited replicative potential, ability to develop blood vessels (angiogenesis), evasion of programmed cell death (apoptosis), self-sufficiency in growth signals, insensitivity to inhibitors of growth, inflammation, tissue invasion and metastasis. In this review we explore the mechanisms by which HMGB1 regulates apoptosis and autophagy in glioma. We also looked at how HMGB1 mediates glioma regression and promotes angiogenesis as well as possible signaling pathways with an attempt to provide potential therapeutic targets for the treatment of glioma.

scholarly journals Critical role of Src-Syk-PLCγ2 signaling in megakaryocyte migration and thrombopoiesis

Blood ◽  
2010 ◽  
Vol 116 (5) ◽  
pp. 793-800 ◽  
Author(s):  
Alexandra Mazharian ◽  
Steve G. Thomas ◽  
Tarvinder S. Dhanjal ◽  
Christopher D. Buckley ◽  
Steve P. Watson
Keyword(s):  
Kinase Inhibitor ◽  
Tyrosine Phosphatase ◽  
Critical Role ◽  
Src Family Kinases ◽  
Surface Glycoprotein ◽  
Platelet Recovery ◽  
Glycoprotein Vi ◽  
Syk Kinase ◽  
And Migration

Migration of megakaryocytes (MKs) from the proliferative osteoblastic niche to the capillary-rich vascular niche is essential for proplatelet formation and platelet release. In this study, we explore the role of surface glycoprotein receptors and signaling proteins in regulating MK migration and platelet recovery after immune-induced thrombocytopenia. We show that spreading and migration of mouse primary bone marrow–derived MKs on a fibronectin matrix are abolished by the Src family kinases inhibitor PP1, the Syk kinase inhibitor R406 and the integrin αIIbβ3 antagonist lotrafiban. We also demonstrate that these responses are inhibited in primary phospholipase C γ2 (PLCγ2)–deficient MKs. Conversely, MK spreading and migration were unaltered in the absence of the collagen receptor, the glycoprotein VI–FcRγ-chain complex. We previously reported a correlation between a defect in MK migration and platelet recovery in the absence of platelet endothelial cell adhesion molecule-1 and the tyrosine phosphatase CD148. This correlation also holds for mice deficient in PLCγ2. This study identifies a model in which integrin signaling via Src family kinases and Syk kinase to PLCγ2 is required for MK spreading, migration, and platelet formation.

scholarly journals The Role of HGF/MET Signaling in Metastatic Uveal Melanoma

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5457
Author(s):  
Ryota Tanaka ◽  
Mizue Terai ◽  
Eric Londin ◽  
Takami Sato
Keyword(s):  
Uveal Melanoma ◽  
Treatment Resistance ◽  
Therapeutic Benefit ◽  
Cellular Functions ◽  
Major Mechanism ◽  
Pathway Activation ◽  
Mesenchymal Epithelial Transition Factor ◽  
And Migration ◽  
Hepatocyte Growth

Hepatocyte growth factor (HGF)/mesenchymal-epithelial transition factor (MET) signaling promotes tumorigenesis and tumor progression in various types of cancer, including uveal melanoma (UM). The roles of HGF/MET signaling have been studied in cell survival, proliferation, cell motility, and migration. Furthermore, HGF/MET signaling has emerged as a critical player not only in the tumor itself but also in the tumor microenvironment. Expression of MET is frequently observed in metastatic uveal melanoma and is associated with poor prognosis. It has been reported that HGF/MET signaling pathway activation is the major mechanism of treatment resistance in metastatic UM (MUM). To achieve maximal therapeutic benefit in MUM patients, it is important to understand how MET signaling drives cellular functions in uveal melanoma cells. Here, we review the HGF/MET signaling biology and the role of HGF/MET blockades in uveal melanoma.

scholarly journals DHCR24 Promotes Melanoma Stem-Like Cells Formation and Mediates Vemurafenib Resistance by Accumulating 27-Hydroxycholesterol

2021 ◽  
Author(s):  
Feiliang Zhong ◽  
Tingting Chen ◽  
Jia Liu ◽  
Ying Wang ◽  
Mingdong Yao ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Treatment Resistance ◽  
Melanoma Cells ◽  
Significant Inhibition ◽  
Cholesterol Homeostasis ◽  
Rna Seq ◽  
Xenograft Mice ◽  
Melanoma Patients ◽  
And Migration

Abstract Background: Melanoma is the most serious skin cancer with gradually increased incidence and poor prognosis mainly as the result of cancer stem cell (CSC) expansion and drug resistance. Some studies have suggested that dysregulated cholesterol homeostasis increasing tumorigenicity and metastasis in cancers. In the present study, our objective was to elucidate the contribution of 24-Dehydrocholesterol reductase (DHCR24) towards melanoma progression and drug resistance.Methods: Immunohistochemistry and HE staining were performed for determing the expression of DHCR24 in melanoma patients, lentivirus perturbation and functional assays were used to evaluate the ability of turmorigenesis of DHCR24 altered melanoma cells and melanoma stem-like cells. RNA sequencing (RNA-seq) and targeted metabolomics were carried out for identifying metabolites which contributes melanoma stem-like cell expansion and vemurafenib treatment resistance.Results: DHCR24 was over-expressed in melanoma patients while knockdown of DHCR24 blocked melanoma cells in S phase and lead to significant inhibition in proliferation and migration. Meanwhile, forced expression of DHCR24 promotes the growth of melanoma cells in xenograft mice. We further demonstrated that DHCR24 promotes the proliferation of melanoma stem-like cell populations by activating Rap1/AKT signaling and result in accumulation of cellular 27-Hydroxycholesterol (27-HC) contents. Next, we validated that both CYP27A1 and 27-HC administration contributed to melanoma stem-like cells formation and vemurafenib resistance through AKT-308/309 phosphorylation. Conclusions: Our data confirmed the oncogenic role of DHCR24 in melanoma stem-like cells proliferation and vemurafenib resistance by regulating 27-HC. These findings established the basis of targeting DHCR24 as a potential therapeutic target for advanced melanoma.

scholarly journals Up-regulation of microRNA-497-5p inhibits colorectal cancer cell proliferation and invasion via targeting PTPN3

2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Sen Hong ◽  
Zhenkun Yan ◽  
Helei Wang ◽  
Lei Ding ◽  
Miaomiao Bi
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Lines ◽  
Tyrosine Phosphatase ◽  
Migration And Invasion ◽  
Clinical Samples ◽  
Aberrant Expression ◽  
Downstream Target ◽  
And Migration

Abstract To investigate the role of microRNA-497-5p (miR-497-5p) in the tumorigenesis of colorectal cancer (CRC), the present study applied qRT-PCR to detect the expression level of miR-497-5p in both clinical samples and CRC cell lines. Furthermore, to specifically evaluate the carcinogenic role of miR-497-5p in CRC, the expression of miR-497-5p was monitored by transfecting with the mimics or inhibitors of miR-497-5p. Transwell assay as well as CCK-8 assay were used to determine the functions of miR-497-5p on cell invasion, migration and proliferation, respectively. miR-497-5p expression was remarkably down-regulated in clinical samples with cancer development as well as in CRC cell lines. Additionally, low miR-497-5p expression was remarkably correlated with higher TNM stage and lymph node metastasis of CRC patients. Up-regulation of miR-497-5p significantly inhibited proliferation, migration, and invasion of LOVO CRC cell line. Conversely, antagonizing miR-497-5p significantly promoted cell proliferation, migration and invasion. Mechanistic analysis revealed that miR-497-5p directly bound to its downstream target, protein tyrosine phosphatase non-receptor type 3 (PTPN3), whose aberrant expression partially reversed inhibition of cell proliferation and migration. Taken together, the present study elucidated the inhibitory role of miR-497-5p in CRC via targeting PTPN3, which potentiated miR-497-5p as a potential therapeutic target for combating CRC.

Credit constraints and Rural Migration: Evidence from Six Villages in Uttar Pradesh

2018 ◽  
Vol 15 (3) ◽  
pp. 389-398
Author(s):  
Ruchi Singh
Keyword(s):  
Credit Constraints ◽  
Uttar Pradesh ◽  
Binary Logistic Regression ◽  
Binary Logistic Regression Model ◽  
Male Migration ◽  
Rural Economies ◽  
And Migration ◽  
The Relationship ◽  
The Empirical Analysis

Rural economies in developing countries are often characterized by credit constraints. Although few attempts have been made to understand the trends and patterns of male out-migration from Uttar Pradesh (UP), there is dearth of literature on the linkage between credit accessibility and male migration in rural Uttar Pradesh. The present study tries to fill this gap. The objective of this study is to assess the role of credit accessibility in determining rural male migration. A primary survey of 370 households was conducted in six villages of Jaunpur district in Uttar Pradesh. Simple statistical tools and a binary logistic regression model were used for analyzing the data. The result of the empirical analysis shows that various sources of credit and accessibility to them play a very important role in male migration in rural Uttar Pradesh. The study also found that the relationship between credit constraints and migration varies across various social groups in UP.

Role of microenvironment on proliferation and migration of an SDHB silenced murine Pheochromocytoma cell line

2017 ◽  
Author(s):  
Serena Martinelli ◽  
Vanessa D'Antongiovanni ◽  
Susan Richter ◽  
Letizia Canu ◽  
Tonino Ercolino ◽  
...  
Keyword(s):  
Cell Line ◽  
Pheochromocytoma Cell ◽  
And Migration ◽  
Proliferation And Migration

Glioblastoma invasion and NMDA receptors: A novel prospect

2019 ◽  
Vol 106 (3) ◽  
pp. 250-260 ◽  
Author(s):  
DN Nandakumar ◽  
P Ramaswamy ◽  
C Prasad ◽  
D Srinivas ◽  
K Goswami
Keyword(s):  
Glutamate Receptors ◽  
Cell Lines ◽  
Intracellular Signaling ◽  
Transcript Level ◽  
Glioblastoma Cells ◽  
Invasion And Migration ◽  
Matrigel Invasion ◽  
Nmdar Activation ◽  
And Migration

Purpose Glioblastoma cells create glutamate-rich tumor microenvironment, which initiates activation of ion channels and modulates downstream intracellular signaling. N-methyl-D-aspartate receptors (NMDARs; a type of glutamate receptors) have a high affinity for glutamate. The role of NMDAR activation on invasion of glioblastoma cells and the crosstalk with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is yet to be explored. Main methods LN18, U251MG, and patient-derived glioblastoma cells were stimulated with NMDA to activate NMDAR glutamate receptors. The role of NMDAR activation on invasion and migration and its crosstalk with AMPAR were evaluated. Invasion and migration of glioblastoma cells were investigated by in vitro trans-well Matrigel invasion and trans-well migration assays, respectively. Expression of NMDARs and AMPARs at transcript level was evaluated by quantitative real-time polymerase chain reaction. Results We determined that NMDA stimulation leads to enhanced invasion in LN18, U251MG, and patient-derived glioblastoma cells, whereas inhibition of NMDAR using MK-801, a non-competitive antagonist of the NMDAR, significantly decreased the invasive capacity. Concordant with these findings, migration was significantly augmented by NMDAR in both cell lines. Furthermore, NMDA stimulation upregulated the expression of GluN2 and GluA1 subunits at the transcript level. Conclusions This study demonstrated the previously unexplored role of NMDAR in invasion of glioblastoma cells. Furthermore, the expression of the GluN2 subunit of NMDAR and the differential overexpression of the GluA1 subunit of AMPAR in both cell lines provide a plausible rationale of crosstalk between these calcium-permeable subunits in the glutamate-rich microenvironment of glioblastoma.

TRIM44 promotes cell proliferation and migration by inhibiting FRK in renal cell carcinoma

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Proliferation ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Lymphatic Invasion ◽  
Cancer Specific Survival ◽  
Candidate Target ◽  
Candidate Target Gene ◽  
And Migration

TRIM44 has oncogenic roles in various cancers. However, TRIM44 expression andits function in renal cell carcinoma (RCC) are still unknown. Here in this study, weinvestigated the clinical significance of TRIM44 and its biological function in RCC.TRIM44 overexpression was significantly associated with clinical M stage, histologictype (clear cell) and presence of lymphatic invasion (P = .047, P = .005, and P = .028,respectively). Moreover, TRIM44 overexpression was significantly associated withpoor prognosis in terms of cancer-specific survival (P = .019). Gain-of-function andloss-of-function studies using TRIM44 and siTRIM44 transfection showed thatTRIM44 promotes cell proliferation and cell migration in two RCC cell lines, Caki1and 769P. To further investigate the role of TRIM44 in RCC, we performed integratedmicroarray analysis in Caki1 and 769P cells and explored the data in the Oncominedatabase. Interestingly, FRK was identified as a promising candidate target gene ofTRIM44, which was downregulated in RCC compared with normal renal tissues. Wefound that cell proliferation was inhibited by TRIM44 knockdown and then recoveredby siFRK treatment. Taken together, the present study revealed the associationbetween high expression of TRIM44 and poor prognosis in

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