scholarly journals The F11 Receptor (F11R)/Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A) in cancer progression

2021 ◽  
Author(s):  
Kamila Czubak-Prowizor ◽  
Anna Babinska ◽  
Maria Swiatkowska
Keyword(s):  
Cancer Progression ◽  
Adhesion Molecule ◽  
Epithelial To Mesenchymal Transition ◽  
Cell Function ◽  
Immunoglobulin Superfamily ◽  
Dependent Manner ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
Transmembrane Glycoprotein ◽  
Tight Junction Formation

AbstractThe F11 Receptor (F11R), also called Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A), is a transmembrane glycoprotein of the immunoglobulin superfamily, which is mainly located in epithelial and endothelial cell tight junctions and also expressed on circulating platelets and leukocytes. It participates in the regulation of various biological processes, as diverse as paracellular permeability, tight junction formation and maintenance, leukocyte transendothelial migration, epithelial-to-mesenchymal transition, angiogenesis, reovirus binding, and platelet activation. Dysregulation of F11R/JAM-A may result in pathological consequences and disorders in normal cell function. A growing body of evidence points to its role in carcinogenesis and invasiveness, but its tissue-specific pro- or anti-tumorigenic role remains a debated issue. The following review focuses on the F11R/JAM-A tissue-dependent manner in tumorigenesis and metastasis and also discusses the correlation between poor patient clinical outcomes and its aberrant expression. In the future, it will be required to clarify the signaling pathways that are activated or suppressed via the F11R/JAM-A protein in various cancer types to understand its multiple roles in cancer progression and further use it as a novel direct target for cancer treatment.

scholarly journals Enhanced osteopontin splicing regulated by RUNX2 is HDAC-dependent and induces invasive phenotypes in NSCLC cells

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Jing Huang ◽  
Siyuan Chang ◽  
Yabin Lu ◽  
Jing Wang ◽  
Yang Si ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
A549 Cells ◽  
Gene Promoter ◽  
Nsclc Cell Line ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Splicing Variant ◽  
Splicing Isoforms

Abstract Background Increased cell mobility is a signature when tumor cells undergo epithelial-to-mesenchymal transition. TGF-β is a key stimulating factor to promote the transcription of a variety of downstream genes to accelerate cancer progression and metastasis, including osteopontin (OPN) which exists in several functional forms as different splicing variants. In non-small cell lung cancer cells, although increased total OPN expression was observed under various EMT conditions, the exact constitution and the underlining mechanism towards the generation of such OPN splicing isoforms was poorly understood. Methods We investigated the possible mechanisms of osteopontin splicing variant and its role in EMT and cancer metastasis using NSCLC cell line and cell and molecular biology techniques. Results In this study, we determined that OPNc, an exon 4 excluded shorter form of Opn gene products, appeared to be more potent to promote cell invasion. The expression of OPNc was selectively increased to higher abundance during EMT following TGF-β induction. The switching from OPNa to OPNc could be enhanced by RUNX2 (a transcription factor that recognizes the Opn gene promoter) overexpression, but appeared to be strictly in a HDAC dependent manner in A549 cells. The results suggested the increase of minor splicing variant of OPNc required both (1) the enhanced transcription from its coding gene driven by specific transcription factors; and (2) the simultaneous modulation or fluctuation of the coupled splicing process that depends to selective classed of epigenetic regulators, predominately HDAC family members. Conclusion Our study not only emphasized the importance of splicing variant for its role in EMT and cancer metastasis, but also helped to understand the possible mechanisms of the epigenetic controls for defining the levels and kinetic of gene splicing isoforms and their generations.

scholarly journals The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1239
Author(s):  
Leila Jahangiri ◽  
Tala Ishola ◽  
Perla Pucci ◽  
Ricky M. Trigg ◽  
Joao Pereira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Regulatory Networks ◽  
Epithelial To Mesenchymal Transition ◽  
Tumour Microenvironment ◽  
Repair Capacity ◽  
Mesenchymal Transition ◽  
Cellular Processes

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

scholarly journals Pyrvinium pamoate inhibits cell proliferation through ROS-mediated AKT-dependent signaling pathway in colorectal cancer

2021 ◽  
Vol 38 (2) ◽  
Author(s):  
Wenqian Zheng ◽  
Jinhui Hu ◽  
Yiming Lv ◽  
Bingjun Bai ◽  
Lina Shan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Signaling Pathway ◽  
Epithelial To Mesenchymal Transition ◽  
Flow Cytometric Analysis ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Dependent Signaling Pathway ◽  
Pyrvinium Pamoate

AbstractThe use of the anthelmintic drug pyrvinium pamoate (PP) in cancer therapy has been extensively investigated in the last decade. PP has been shown to have an inhibitory effect in colorectal cancer (CRC), but the underlying mechanism remains elusive. We aimed to investigate the antitumor activity and mechanisms of PP in CRC. In the present study, we used CCK-8 assays, colony formation assays, and western blotting to reveal that PP effectively suppressed CRC cell proliferation and the AKT-dependent signaling pathway in a concentration-dependent and time-dependent manner. Flow cytometric analysis and fluorescence microscopy demonstrated that PP increased intracellular reactive oxygen species (ROS) accumulation. We found that the inhibitory effect of PP on cell proliferation and AKT protein expression induced by PP could be partially reversed by N-acetyl-l-cysteine (NAC), an ROS scavenger. In addition, the results also demonstrated that PP inhibited cell migration by modulating epithelial-to-mesenchymal transition (EMT)-related proteins, including E-cadherin and vimentin. In conclusion, our data suggested that PP effectively inhibited cell proliferation through the ROS-mediated AKT-dependent signaling pathway in CRC, further providing evidence for the use of PP as an antitumor agent.

scholarly journals Behaviour of a sperm surface transmembrane glycoprotein basigin during epididymal maturation and its role in fertilization in mice

Reproduction ◽  
2002 ◽  
pp. 435-444 ◽  
Author(s):  
DK Saxena ◽  
T Oh-Oka ◽  
K Kadomatsu ◽  
T Muramatsu ◽  
K Toshimori
Keyword(s):  
Fertilization Rate ◽  
Sperm Head ◽  
Immunoglobulin Superfamily ◽  
Dependent Manner ◽  
Transmembrane Glycoprotein ◽  
Middle Piece ◽  
Epididymal Maturation ◽  
Principal Piece ◽  
Cauda Epididymidis ◽  
Dose Dependent

Basigin (bsg) is a transmembrane glycoprotein belonging to an immunoglobulin superfamily and is localized on the surface of the sperm tail. The behaviour of bsg during epididymal maturation and its role in fertilization were examined using an anti-bsg antibody. Spermatozoa from caput, corpus and cauda epididymides were immunostained by indirect immunofluorescence (IIF). Immunostaining revealed that bsg is localized on the principal piece of caput spermatozoa and the molecule was found on the middle piece during transit in the corpus and cauda epididymides. Concomitantly, the molecular mass of bsg was reduced from 37 kDa (testis) to 26 kDa (cauda epididymidis). IVF experiments were designed to assess the effect of anti-bsg antibody on the fertilization events. Anti-bsg antibody significantly inhibited primary binding to the cumulus-invested oocytes with intact zonae pellucidae in a dose-dependent manner. Consequently, the fertilization rate of cumulus-invested oocytes with intact zonae pellucidae was also inhibited. The bsg molecule was also detected on the head of live capacitated spermatozoa by IIF under IVF conditions. These findings indicate that testicular bsg is a glycosylated protein that undergoes molecular processing and deglycosylation during its transit in the epididymis. The bsg molecule that was detected on the sperm head after capacitation may facilitate the primary binding or might be involved in distinct events required for primary binding of spermatozoa to the zona pellucida during capacitation and sperm-cumulus interaction.

scholarly journals Sp1-Induced Upregulation of LBX2-AS1 Aggravates The Progression of Glioblastoma By Targeting The miR-491-5p/LIF Axis

2021 ◽  
Author(s):  
Wentao Li ◽  
Ismatullah Soufiany ◽  
Xiao Lyu ◽  
Lin Zhao ◽  
Chenfei Lu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Stat3 Signaling ◽  
Regulatory Effects

Abstract Background: Mounting evidences have shown the importance of lncRNAs in tumorigenesis and cancer progression. LBX2-AS1 is an oncogenic lncRNA that has been found abnormally expressed in gastric cancer and lung cancer samples. Nevertheless, the biological function of LBX2-AS1 in glioblastoma (GBM) and potential molecular mechanism are largely unclear. Methods: Relative levels of LBX2-AS1 in GBM samples and cell lines were detected by qRT-PCR and FISH. In vivo and in vitro regulatory effects of LBX2-AS1 on cell proliferation, epithelial-to-mesenchymal transition (EMT) and angiogenesis in GBM were examined through xenograft models and functional experiments, respectively. The interaction between Sp1 and LBX2-AS1 was assessed by ChIP. Through bioinformatic analyses, dual-luciferase reporter assay, RIP and Western blot, the regulation of LBX2-AS1 and miR-491-5p on the target gene leukemia Inhibitory factor (LIF) was identified. Results: LBX2-AS1 was upregulated in GBM samples and cell lines, and its transcription was promoted by binding to the transcription factor Sp1. As a lncRNA mainly distributed in the cytoplasm, LBX2-AS1 upregulated LIF, and activated the LIF/STAT3 signaling by exerting the miRNA sponge effect on miR-491-5p, thus promoting cell proliferation, EMT and angiogenesis in GBM. Besides, LBX2-AS1 was unfavorable to the progression of glioma and the survival. Conclusion: Upregulated by Sp1, LBX2-AS1 promotes the progression of GBM by targeting the miR-491-5p/LIF axis. It is suggested that LBX2-AS1 may be a novel diagnostic biomarker and therapeutic target of GBM.

scholarly journals PKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression

2021 ◽  
Vol 11 ◽  
Author(s):  
Qingmin Sun ◽  
Mengyun Yuan ◽  
Hongxing Wang ◽  
Xingxing Zhang ◽  
Ruijuan Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Progression ◽  
Cancer Metastasis ◽  
Nuclear Translocation ◽  
Aerobic Glycolysis ◽  
Metabolic Reprogramming ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Gastric Cancer Cells ◽  
Mesenchymal Transition

Gastric cancer is the third leading cause of cancer death worldwide. Traditional Chinese medicine (TCM) is increasingly extensively applied as a complementary therapy for gastric cancer (GC) in China, which shows unique advantages in preventing gastric cancer metastasis. Previous study indicates modified Jian-pi-yang-zheng (mJPYZ) decoction inhibit the progression of gastric cancer by regulating tumor-associated macrophages (TAM). However, it is unclear whether mJPYZ can affect metabolic reprogramming of gastric cancer cells. Here, we showed that mJPYZ effectively attenuated GC cells proliferation, migration and invasion. Meantime, mJPYZ reduced the aerobic glycolysis level of GC cells in vivo and in vitro by regulating the expression and nuclear translocation of PKM2. Overexpression of PKM2 that could reverse the inhibitory effect of mJPYZ, migration and epithelial to mesenchymal transition (EMT). Our results showed PKM2/HIF-1α signaling was the key metabolic regulator of mJPYZ in GC cells. In summary, our present study suggested that abnormal PKM2 is required for maintaining the malignant phenotype of GC cells. The TCM decoction mJPYZ inhibited GC cells growth and EMT by reducing of glycolysis in PKM2 dependent manner. This evidence expanded our understanding of the anti-tumor mechanism of mJPYZ and further indicated mJPYZ a potential anti-tumor agent for GC patients.Chemical Compounds Studied in this ArticleRutin (PubChem CID: 5280805); Lobetyolin (PubChem CID: 53486204); Calycosin-7-glucoside (PubChem CID: 71571502); Formononetin (PubChem CID: 5280378); Calycosin (PubChem CID: 5280448); Ononin (PubChem CID: 442813); P-Coumaric Acid (PubChem CID: 637542).

scholarly journals Embigin Promotes Prostate Cancer Progression by S100A4-Dependent and-Independent Mechanisms

Cancers ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 239 ◽  
Author(s):  
I Ruma ◽  
Rie Kinoshita ◽  
Nahoko Tomonobu ◽  
Yusuke Inoue ◽  
Eisaku Kondo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Cancer Progression ◽  
Immunoglobulin Superfamily ◽  
Prostate Cancer Progression ◽  
Transmembrane Glycoprotein ◽  
Mtorc1 Signaling ◽  
Ampk Activity ◽  
In Vivo Growth

Embigin, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, is involved in prostate and mammary gland development. As embigin’s roles in cancer remain elusive, we studied its biological functions and interaction with extracellular S100A4 in prostate cancer progression. We found by a pull-down assay that embigin is a novel receptor for S100A4, which is one of the vital cancer microenvironment milleu. Binding of extracellular S100A4 to embigin mediates prostate cancer progression by inhibition of AMPK activity, activation of NF-κB, MMP9 and mTORC1 signaling, and inhibition of autophagy, which increase prostate cancer cell motility. We also found that embigin promotes prostate cancer growth, spheroid- and colony-forming ability, and survival upon chemotherapy independently of S100A4. An in vivo growth mouse model confirmed the importance of embigin and its cytoplasmic tail in mediating prostate tumor growth. Moreover, embigin and p21WAF1 can be used to predict survival of prostate cancer patients. Our results demonstrated for the first time that the S100A4-embigin/AMPK/mTORC1/p21WAF1 and NF-κB/MMP9 axis is a vital oncogenic molecular cascade for prostate cancer progression. We proposed that embigin and p21WAF1 could be used as prognostic biomarkers and a strategy to inhibit S100A4-embigin binding could be a therapeutic approach for prostate cancer patients.

scholarly journals Jagged1-mediated Notch activation induces epithelial-to-mesenchymal transition through Slug-induced repression of E-cadherin

2007 ◽  
Vol 204 (12) ◽  
pp. 2935-2948 ◽  
Author(s):  
Kevin G. Leong ◽  
Kyle Niessen ◽  
Iva Kulic ◽  
Afshin Raouf ◽  
Connie Eaves ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Poor Prognosis ◽  
Epithelial To Mesenchymal Transition ◽  
Breast Tumors ◽  
Aberrant Expression ◽  
Mesenchymal Transition ◽  
Slug Expression ◽  
Tumor Growth And Metastasis ◽  
Notch Activation ◽  
E Cadherin

Aberrant expression of Jagged1 and Notch1 are associated with poor outcome in breast cancer. However, the reason that Jagged1 and/or Notch overexpression portends a poor prognosis is unknown. We identify Slug, a transcriptional repressor, as a novel Notch target and show that elevated levels of Slug correlate with increased expression of Jagged1 in various human cancers. Slug was essential for Notch-mediated repression of E-cadherin, which resulted in β-catenin activation and resistance to anoikis. Inhibition of ligand-induced Notch signaling in xenografted Slug-positive/E-cadherin–negative breast tumors promoted apoptosis and inhibited tumor growth and metastasis. This response was associated with down-regulated Slug expression, reexpression of E-cadherin, and suppression of active β-catenin. Our findings suggest that ligand-induced Notch activation, through the induction of Slug, promotes tumor growth and metastasis characterized by epithelial-to-mesenchymal transition and inhibition of anoikis.

scholarly journals Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression

2016 ◽  
Vol 113 (48) ◽  
pp. E7749-E7758 ◽  
Author(s):  
Roberto Rangel ◽  
Song-Choon Lee ◽  
Kenneth Hon-Kim Ban ◽  
Liliana Guzman-Rojas ◽  
Michael B. Mann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Epithelial To Mesenchymal Transition ◽  
Breast Cancer Subtype ◽  
Clinical Importance ◽  
Transposon Mutagenesis ◽  
Phosphatase And Tensin Homolog ◽  
Mesenchymal Transition ◽  
Tensin Homolog ◽  
Cancer Subtype

Triple-negative breast cancer (TNBC) has the worst prognosis of any breast cancer subtype. To better understand the genetic forces driving TNBC, we performed a transposon mutagenesis screen in a phosphatase and tensin homolog (Pten) mutant mice and identified 12 candidate trunk drivers and a much larger number of progression genes. Validation studies identified eight TNBC tumor suppressor genes, including the GATA-like transcriptional repressorTRPS1. Down-regulation ofTRPS1in TNBC cells promoted epithelial-to-mesenchymal transition (EMT) by deregulating multiple EMT pathway genes, in addition to increasing the expression ofSERPINE1andSERPINB2and the subsequent migration, invasion, and metastasis of tumor cells. Transposon mutagenesis has thus provided a better understanding of the genetic forces driving TNBC and discovered genes with potential clinical importance in TNBC.

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