scholarly journals Tumor-Associated Macrophages (TAMs) in Colorectal Cancer (CRC): From Mechanism to Therapy and Prognosis

2021 ◽  
Vol 22 (16) ◽  
pp. 8470
Author(s):  
Hui Wang ◽  
Tian Tian ◽  
Jinhua Zhang
Keyword(s):  
Colorectal Cancer ◽  
Clinical Care ◽  
Inflammatory Cells ◽  
Genetic Alterations ◽  
Tumor Associated Macrophages ◽  
Invasion And Migration ◽  
Complex Process ◽  
Incidence And Mortality ◽  
And Migration

Colorectal cancer (CRC) is a malignant tumor in the digestive system whose incidence and mortality is high-ranking among tumors worldwide. The initiation and progression of CRC is a complex process involving genetic alterations in cancer cells and multiple factors from the surrounding tumor cell microenvironment. As accumulating evidence has shown, tumor-associated macrophages (TAMs)—as abundant and active infiltrated inflammatory cells in the tumor microenvironment (TME)—play a crucial role in CRC. This review focuses on the different mechanisms of TAM in CRC, including switching of phenotypical subtypes; promoting tumor proliferation, invasion, and migration; facilitating angiogenesis; mediating immunosuppression; regulating metabolism; and interacting with the microbiota. Although controversy remains in clinical evidence regarding the role of TAMs in CRC, clarifying their significance in therapy and the prognosis of CRC may shed new light on the optimization of TAM-centered approaches in clinical care.

scholarly journals MiR-208a-3p functions as an oncogene in colorectal cancer by targeting PDCD4

2019 ◽  
Vol 39 (4) ◽  
Author(s):  
Henglan Wu ◽  
Lele Xu ◽  
Yaou Chen ◽  
Chunfang Xu
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Death ◽  
Biological Function ◽  
Invasion And Migration ◽  
Functional Assays ◽  
Direct Target ◽  
And Migration ◽  
Cell Death Protein

AbstractAccumulating evidences have shown microRNAs (miRNAs) play important roles in the progression of human cancers including colorectal cancer (CRC). However, the biological function and molecular mechanism of miRNAs in CRC still remains to be further investigated. Using microarray, we found and confirmed that miR-208a-3p was up-regulated in CRC tissues. Its high expression was statistically associated with distant metastasis and TNM stage. Functional assays revealed inhibition of miR-208a-3p suppressed proliferation, invasion and migration, and induced cell apoptosis of CRC cells. Moreover, we identified programmed cell death protein 4 (PDCD4), a well-known tumor suppressor, is a direct target of miR-208a-3p. We also found that overexpression of PDCD4 suppressed cell proliferation, invasion, and migration. Importantly, silencing of PDCD4 efficiently abrogated the promoting effects on CRC cells proliferation, invasion, and migration caused by inhibition of miR-208a-3p. Our findings confirmed the oncogenic role of miR-208a-3p via targeting PDCD4 in CRC, identifying miR-208a-3p as a potential diagnosis and therapeutic biomarker for CRC.

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.

ERK5 and its role in tumour development

2012 ◽  
Vol 40 (1) ◽  
pp. 251-256 ◽  
Author(s):  
Pamela A. Lochhead ◽  
Rebecca Gilley ◽  
Simon J. Cook
Keyword(s):  
Mitogen Activated Protein Kinase ◽  
Invasion And Migration ◽  
Extracellular Signal Regulated Kinase ◽  
Protein Levels ◽  
Extracellular Signal ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Tumour Cell Invasion ◽  
And Migration

The MEK5 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 5]/ERK5 pathway is the least well studied MAPK signalling module. It has been proposed to play a role in the pathology of cancer. In the present paper, we review the role of the MEK5/ERK5 pathway using the ‘hallmarks of cancer’ as a framework and consider how this pathway is deregulated. As well as playing a key role in endothelial cell survival and tubular morphogenesis during tumour neovascularization, ERK5 is also emerging as a regulator of tumour cell invasion and migration. Several oncogenes can stimulate ERK5 activity, and protein levels are increased by a novel amplification at chromosome locus 17p11 and by down-regulation of the microRNAs miR-143 and miR-145. Together, these finding underscore the case for further investigation into understanding the role of ERK5 in cancer.

scholarly journals FGFR3 promotes the growth and malignancy of melanoma by influencing EMT and the phosphorylation of ERK, AKT, and EGFR

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Lei Li ◽  
Shuai Zhang ◽  
Hao Li ◽  
Haiyan Chou
Keyword(s):  
Cell Proliferation ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Colony Formation ◽  
Caspase 3 ◽  
Growth Factor Receptor ◽  
Invasion And Migration ◽  
Node Metastasis ◽  
And Migration

Abstract Background Overexpression of fibroblast growth factor receptor 3 (FGFR3) has been linked to tumor progression in many types of cancer. The role of FGFR3 in melanoma remains unclear. In this study, we aimed to uncover the role of FGFR3 in the growth and metastasis of melanoma. Methods FGFR3 knockdown and overexpression strategies were employed to investigate the effects of FGFR3 on colony formation, cell apoptosis, proliferation, migration, and in vitro invasion, along with the growth and metastasis of melanoma in a xenografts mouse model. The protein expression levels of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), epidermal growth factor receptor (EGFR), and epithelial-mesenchymal transition (EMT) markers were determined by Western blot analysis. Results The mRNA expression of FGFR3 was higher in melanoma tissues than normal healthy tissues. FGFR3 expression in cutaneous malignant melanoma (CMM) tissues was positively correlated with the Breslow thickness and lymph node metastasis. In A357 cells, knockdown of the FGFR3 gene decreased the colony formation ability, cell proliferation, invasion, and migration, but increased the caspase 3 activity and the apoptosis rate; overexpression of FGFR3 increased the colony formation ability, cell proliferation, invasion, and migration, but decreased the caspase 3 activity and apoptosis rates. FGFR3 knockdown also upregulated E-cadherin, downregulated N-cadherin and vimentin, and decreased the phosphorylation levels of ERK, AKT, and EGFR. In the MCC xenografts mice, knockdown of FGFR3 decreased tumor growth and metastasis. Conclusions FGFR3, which is highly expressed in CMM tissues, is correlated with increased Breslow thickness and lymph node metastasis. FGFR3 promotes melanoma growth, metastasis, and EMT behaviors, likely by affecting the phosphorylation levels of ERK, AKT, and EGFR.

scholarly journals miR-17-5p promotes the invasion and migration of colorectal cancer by regulating HSPB2

2020 ◽  
Author(s):  
Wei fang Yu ◽  
Jia Wang ◽  
Chao Li ◽  
Mingda Xuan ◽  
Shuangshuang Han ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Lymph Node ◽  
Target Genes ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Normal Tissues ◽  
Node Metastasis ◽  
Rescue Experiment ◽  
And Migration

Abstract Background: MicroRNA (miRNA) can affect tumor progression by regulating cell proliferation, apoptosis and metastasis. After miRNA microarray chip analysis of colorectal cancer (CRC) tissues and adjacent normal tissues, a significant upregulation of miR-17-5p expression was found in CRC tissues. However, the underlying mechanism of miR-17-5p in CRC is still unclear.Methods: The levels of miR-17-5p in 47 paired CRC and adjacent normal tissue samples were determined by quantitative real-time PCR (qRT-PCR). CCK-8, colony formation, flow cytometry and transwell assays were used to explore the biological effects of miR-17-5p on CRC cells. In addition, the transcriptome sequencing and miRNA target prediction software were employed to identify targets of miR-17-5p. Luciferase reporter detection was used to demonstrate the direct binding of target genes by miR-17-5p. The rescue experiment was conducted to investigate the biological function of target genes and regulatory mechanism of miR-17-5p on target genes.Results: The expression of miR-17-5p was significantly higher in CRC tissues than in adjacent normal tissues. In CRC group, the expression of miR-17-5p in cancer tissues with lymph node metastasis was higher compared with those without lymph node metastasis. Overexpression of miR-17-5p inhibited CRC cell apoptosis, as well as promoting proliferation, migration and invasion. We hypothesized that HSPB2 might be a target gene of miR-17-5p and validated for the first time that miR-17-5p binds directly to the 3’-UTR of HSPB2. In the rescue experiment, the tumor suppressive effect of HSPB2 was detected and miR-17-5p could promote cell proliferation, migration and invasion by targeting HSPB2.Conclusion: MiR-17-5p promotes invasion and migration by inhibiting HSPB2 in CRC, thereby implicating its potential as a novel diagnostic biomarker and therapeutic target for CRC.

scholarly journals LncRNA CRNDE Promoted Colorectal Cancer Cells Reisitance To Paclitaxel Through Wnt/β-Catenin Signaling Pathway

2021 ◽  
Author(s):  
Rui Ma ◽  
Chuan-yang Yu ◽  
Xiang Tao ◽  
Zhi Yang ◽  
Qi Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Colorectal Neoplasia ◽  
Cancer Treatments ◽  
Sw620 Cell ◽  
Invasion And Migration ◽  
Over Expression ◽  
Colorectal Cancer Cells ◽  
Sw620 Cells ◽  
And Migration

Abstract Background The lncRNA colorectal neoplasia differentially expressed (lncRNA CRNDE) is commonly over-expressed in different human cancers and involved in different biological functions. Paclitaxel(PTX) is a tricyclic diterpenoid compound which often used as a natural anticancer drugs in cancer treatments. Although there have many research reports about the mechanisms of LncRNA involved in PTX treatment, there are no any research about lncRNA CRNDE and PTX resistance in colorectal cancer. The purpose of this study is to investigate the mechanisims of LncRNA CRNDE involving PTX resistance in colorectal cancer. Results We constructed lncRNA CRNDE over-expression vector and transfected it into SW620 cell. CCK8, Transwell experiments proved that over-expression of lnc CRNDE increased SW620 cells proliferation and invasion, while the si-CRNDE group was significantly decreased. over-expression CRNDE can significantly up-regulate β-catenin, c-myc, APC and Axin2 expression and affect the expression of cyclinD1 and CDK4 after treated with PTX. Conclusion lncRNA CRNDE promotes CRCs proliferation, invasion and migration. Over-expression of LncRNA CRNDE enhanced the reisitance of CRC to PTX through inhibition of Wnt/ β-catenin signaling pathway.

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