Role of S100 Proteins in Colorectal Carcinogenesis

The family of S100 proteins represents 25 relatively small (9–13 kD) calcium binding proteins. These proteins possess a broad spectrum of important intracellular and extracellular functions. Colorectal cancer is the third most common cancer in men (after lung and prostate cancer) and the second most frequent cancer in women (after breast cancer) worldwide. S100 proteins are involved in the colorectal carcinogenesis through different mechanisms: they enable proliferation, invasion, and migration of the tumour cells; furthermore, S100 proteins increase angiogenesis and activate NF-κβsignaling pathway, which plays a key role in the molecular pathogenesis especially of colitis-associated carcinoma. The expression of S100 proteins in the cancerous tissue and serum levels of S100 proteins might be used as a precise diagnostic and prognostic marker in patients with suspected or already diagnosed colorectal neoplasia. Possibly, in the future, S100 proteins will be a therapeutic target for tailored anticancer therapy.

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Glioblastoma invasion and NMDA receptors: A novel prospect

Physiology International ◽

10.1556/2060.106.2019.22 ◽

2019 ◽

Vol 106 (3) ◽

pp. 250-260 ◽

Cited By ~ 3

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.

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ERK5 and its role in tumour development

Biochemical Society Transactions ◽

10.1042/bst20110663 ◽

2012 ◽

Vol 40 (1) ◽

pp. 251-256 ◽

Cited By ~ 50

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.

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Circulating inflammation markers and colorectal adenoma risk

Carcinogenesis ◽

10.1093/carcin/bgz027 ◽

2019 ◽

Vol 40 (6) ◽

pp. 765-770 ◽

Cited By ~ 1

Author(s):

Wen-Yi Huang ◽

Sonja I Berndt ◽

Meredith S Shiels ◽

Hormuzd A Katki ◽

Anil K Chaturvedi ◽

...

Keyword(s):

Colorectal Adenoma ◽

Statistical Tests ◽

Colorectal Neoplasia ◽

Serum Levels ◽

Colorectal Carcinogenesis ◽

Inflammation Markers ◽

Ovarian Cancer Screening ◽

Cysteine Motif ◽

Chemokine Ligand ◽

Incident Cases

Abstract Inflammation is a driver of colorectal neoplasia; however, what particular inflammatory processes play a role in early carcinogenesis are unclear. We compared serum levels of 78 inflammation markers between 171 pathologically confirmed colorectal adenoma cases (including 48 incident cases) and 344 controls within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We used weighted multivariable logistic regression to compute odds ratio (OR) and 95% confidence interval (CI). We found 14 markers associated with risk of adenoma overall; three of these were also associated with incident adenoma: CC-chemokine cysteine motif chemokine ligand 20 (CCL20) [overall adenoma fourth versus first quartile: OR 4.8, 95% CI 2.0–12, Ptrend 0.0007; incident adenoma third versus first tertile: OR 4.6, 95% CI 1.0–22, Ptrend 0.03], growth-related gene oncogene products (GRO) [OR 3.8, 95% CI 1.6–9.3, Ptrend 0.006 and OR 3.6, 95% CI 1.1–12, Ptrend 0.04, respectively] and insulin [OR 2.9, 95% CI 0.8–10, Ptrend 0.05 and OR 7.8, 95% CI 1.3–46, Ptrend 0.03, respectively]. All statistical tests were two-sided. These results provide important new evidence implicating CCL20- and GRO-related pathways in early colorectal carcinogenesis and further support a role for insulin.

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

BMC Cancer ◽

10.1186/s12885-019-6161-8 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 6

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22168470 ◽

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.

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

10.21203/rs.3.rs-858244/v1 ◽

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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MiR-125b-5p Inhibited The Progression of Hepatoblastoma As A Shared miRNA of The lncRNA NEAT1 and YES1

10.21203/rs.3.rs-49445/v1 ◽

2020 ◽

Author(s):

Zhu Jin ◽

Yutong Chen ◽

Yuchen Mao ◽

Mingjuan Gao ◽

Zebing Zheng ◽

...

Keyword(s):

Clinicopathological Characteristics ◽

Luciferase Reporter ◽

Tumor Growth Inhibition ◽

Invasion And Migration ◽

In Vivo Experiments ◽

Reporter Assays ◽

And Migration ◽

Relationship Of

Abstract Background: microRNAs have been studied widely in hepatoblastoma. However, the role of miR-125b-5p and its relationship with the lncRNA sNEAT1 and YES1 in hepatoblastoma have not been reported previously. We aimed to reveal the role of NEAT1/miR-125b-5p/YES1 in the progression of hepatoblastoma.Methods: We collected tumor tissues and their adjacent tissues from 12 hepatoblastoma patients. qRT-PCR was applied to detect the expression of miR-125b-5p, and the relationship of miR-125b-5p with clinicopathological characteristics was analyzed. Dual luciferase reporter assays and RNA pull down assays were used to identify the relationships among NEAT1, miR-125b-5p and YES1. CCK8, Transwell assays and wound healing assays were used to examine cell viability, invasion and migration. In vivo experiments were also applied to detect the effect of miR-125b-5p on hepatoblastoma.Results: miR-125b-5p was significantly downregulated in hepatoblastoma tissue and cells. The higher the PRETEXT grade, the lower the miR-125b-5p level. NEAT1 could bind to miR-125b-5p and inhibit its expression. miR-125b-5p could target YES1 and inhibit its expression. Overexpression of miR-125b-5p decreased the proliferation, invasion, and migratory ability of hepatoblastoma cells. YES1 could rescue the above effects. At the same time, overexpression of miR-125b-5p resulted in decreased YES1 and tumor growth inhibition in vivo.Conclusion: miR-125b-5p acted as a shared miRNA of NEAT1 and YES1 in hepatoblastoma. Overexpression of miR-125b-5p could target YES1 and inhibit its expression, therefore inhibiting the progression of hepatoblastoma.

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miR-216a-5p Suppresses the Proliferation, Invasion and Migration of Fibroblast-Like Synoviocyte in Rheumatoid Arthritis by Targeting Zinc Finger and BTB Domain-Containing Protein 2 (ZBTB2)

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2021.2589 ◽

2021 ◽

Vol 11 (5) ◽

pp. 896-902

Author(s):

Jinwei Zhao ◽

Ling Li

Keyword(s):

Rheumatoid Arthritis ◽

Cell Proliferation ◽

Zinc Finger ◽

Cell Counting ◽

Luciferase Reporter ◽

Healthy Controls ◽

Invasion And Migration ◽

Btb Domain ◽

And Migration

MicroRNAs have been reported to be associated with the initiation and progression of rheumatoid arthritis (RA). miR-216a-5p, one of the miRNAs, is involved in cancer cell proliferation, invasion and migration. However, the role of miR-216a-5p in RA remains to be explored. The expressions of miR-216a-5p and zinc finger and BTB domain-containing protein 2 (ZBTB2) in fibroblast-like synoviocytes (FLS) of RA or healthy controls were detected by qRT-PCR and western blot analysis. Transfection of overexpressed and silenced miR-216a-5p were performed to explore the functional role of miR-216a-5p in RA-FLS. Cell Counting Kit-8 (CCK-8) assay and transwell assay were employed to assess cell proliferation and cell invasion, respectively. Moreover, luciferase reporter assay was executed to verify the combination of miR-216a-5p and ZBTB2. The results showed that miR-216a-5p expression in RA-FLS was downregulated than healthy controls. Overexpres-sion of miR-216a-5p inhibited RA-FLS cell proliferation, invasion and migration, while miR-216a-5p silencing revealed the opposite results. In addition, ZBTB2 was identified to be a direct target of miR-216a-5p in RA-FLS and its expression was higher than that in healthy controls. Rescue experiments revealed that ZBTB2 overexpression reversed the effects of miR-216a-5p on the proliferation, invasion and migration of RA-FLS. These data indicated the suppressive role of miR-216a-5p in RA-FLS via the regulation of ZBTB2, suggesting that miR-216a-5p and ZBTB2 may be the new targets for the treatment of RA.

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BK polyomavirus infection promotes growth and aggressiveness in bladder cancer

Virology Journal ◽

10.1186/s12985-020-01399-7 ◽

2020 ◽

Vol 17 (1) ◽

Cited By ~ 2

Author(s):

Yigang Zeng ◽

Jiajia Sun ◽

Juan Bao ◽

Tongyu Zhu

Keyword(s):

Bladder Cancer ◽

Signaling Pathway ◽

Epithelial Mesenchymal Transition ◽

Cell Model ◽

Mesenchymal Transition ◽

Invasion And Migration ◽

Urothelial Carcinomas ◽

Bk Polyomavirus ◽

And Migration

Abstract Background Recent studies have confirmed the integration of the BK polyomavirus (BKPyV) gene into the cellular genome of urothelial carcinomas in transplant recipients, further confirming the correlation between BKPyV and urothelial carcinomas after transplantation. However, the role BKPyV infections play in the biological function of bladder cancer remains unclear. Methods We developed a BKPyV-infected bladder cancer cell model and a mice tumor model to discuss the role of BKPyV infections. Results Our research proves that BKPyV infections promote the proliferation, invasion and migration of bladder cancer cells, while the activation of β-catenin signaling pathway is one of its mediation mechanisms. Conclusions We first described BKPyV infection promotes the proliferation, invasion and migration of bladder cancer. We verified the role of β-catenin signaling pathway and Epithelial-Mesenchymal Transition effect in BKPyV-infected bladder cancer. These results provide meaningful information towards the diagnosis and treatment of clinical bladder cancer.

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Up-regulation of miRNA-148a inhibits proliferation, invasion, and migration while promoting apoptosis of cervical cancer cells by down-regulating RRS1

Bioscience Reports ◽

10.1042/bsr20181815 ◽

2019 ◽

Vol 39 (5) ◽

Cited By ~ 3

Author(s):

Ying Zhang ◽

Bingmei Sun ◽

Lianbin Zhao ◽

Zhengling Liu ◽

Zonglan Xu ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Cell Line ◽

Hela Cells ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Invasion And Migration ◽

Cervical Cancer Cells ◽

And Migration

Abstract The purpose of the present study is to figure out the role of miRNA-148a (miR-148a) in growth, apoptosis, invasion, and migration of cervical cancer cells by binding to regulator of ribosome synthesis 1 (RRS1). Cervical cancer and adjacent normal tissues, as well as cervical cancer cell line Caski, HeLa, C-33A, and normal cervical epithelial cell line H8 were obtained to detect the expression of miR-148a and RRS1. Relationship between miR-148a and RRS1 expression with clinicopathological characteristics was assessed. The selected Caski and HeLa cells were then transfected with miR-148a mimics, miR-148a inhibitors or RRS1 siRNA to investigate the role of miR-148a and RRS1 on proliferation, apoptosis, colony formation, invasion, and migration abilities of cervical cancer cells. Bioinformatics information and dual luciferase reporter gene assay was for used to detect the targetting relationship between miR-148a and RRS1. Down-regulated miR-148a and up-regulated RRS1 were found in cervical cancer tissues and cells. Down-regulated miR-148a and up-regulated RRS1 are closely related with prognostic factors of cervical cancer. RRS1 was determined as a target gene of miR-148a and miR-148a inhibited RRS1 expression in cervical cancer cells. Up-regulation of miR-148a inhibited cell proliferation, migration, and invasion while promoting apoptosis in Caski and HeLa cells. Our study suggests that miR-148a down-regulates RRS1 expression, thereby inhibiting the proliferation, migration, and invasion while promoting cell apoptosis of cervical cancer cells.

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