scholarly journals Polycystins in Colorectal Cancer

2018 ◽  
Vol 20 (1) ◽  
pp. 104 ◽  
Author(s):  
Antonios Gargalionis ◽  
Efthimia Basdra ◽  
Athanasios Papavassiliou
Keyword(s):  
Colorectal Cancer ◽  
Calcium Influx ◽  
Cellular Functions ◽  
Selective Treatment ◽  
Adhesion Protein ◽  
Protein Molecules ◽  
Transduction Mechanisms ◽  
Novel Biomarkers ◽  
And Migration ◽  
Focal Adhesion Protein

Cell and extracellular matrix (ECM) biomechanics emerge as a distinct feature during the development and progression of colorectal cancer (CRC). Polycystins are core mechanosensitive protein molecules that mediate mechanotransduction in a variety of epithelial cells. Polycystin-1 (PC1) and polycystin-2 (PC2) are engaged in signal transduction mechanisms and during alterations in calcium influx, which regulate cellular functions such as proliferation, differentiation, orientation, and migration in cancer cells. Recent findings implicate polycystins in the deregulation of such functions and the formation of CRC invasive phenotypes. Polycystins participate in all aspects of the cell’s biomechanical network, from the perception of extracellular mechanical cues to focal adhesion protein and nuclear transcriptional complexes. Therefore, polycystins could be employed as novel biomarkers and putative targets of selective treatment in CRC.

scholarly journals RANTES induces tyrosine kinase activity of stably complexed p125FAK and ZAP-70 in human T cells.

1996 ◽  
Vol 184 (3) ◽  
pp. 873-882 ◽  
Author(s):  
K B Bacon ◽  
M C Szabo ◽  
H Yssel ◽  
J B Bolen ◽  
T J Schall
Keyword(s):  
T Cells ◽  
Tyrosine Kinase ◽  
Focal Adhesion ◽  
Cell Activation ◽  
Focal Adhesions ◽  
Adhesion Protein ◽  
Human T Cells ◽  
Multiple Protein ◽  
Transduction Mechanisms ◽  
Focal Adhesion Protein

The chemokine RANTES is a chemoattractant and activating factor for T lymphocytes. Investigation of the signal transduction mechanisms induced by RANTES in T cells revealed tyrosine phosphorylation of multiple protein species with prominent bands at 70-85 and 120-130 kD. Immunoprecipitation and Western analyses revealed that a protein of 125 kD was identical to the focal adhesion kinase (FAK) pp125FAK. RANTES stimulated phosphorylation of FAK as early as 30 seconds and immunoblots using antiphosphotyrosine monoclonal antibodies revealed that there was consistent phosphorylation of a 68-70 kD species in the pp125FAK immunoprecipitates. Immunoblotting and kinase assays showed this to be two separate proteins, the tyrosine kinase zeta-associated protein (ZAP) 70, and the focal adhesion protein paxillin. These results indicate a potentially important role for RANTES in the generation of T cell focal adhesions and subsequent cell activation via a molecular complex containing FAK, ZAP-70, and paxillin.

scholarly journals Dual phenotype of MDA-MB-468 cancer cells reveals mutual regulation of tensin3 and adhesion plasticity

2017 ◽  
Author(s):  
Astrid Veβ ◽  
Ulrich Blache ◽  
Laura Leitner ◽  
Angela R.M. Kurz ◽  
Anja Ehrenpfordt ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Focal Adhesion ◽  
Three Dimensional ◽  
Suspension Cells ◽  
Adhesion Protein ◽  
Cell Matrix ◽  
Mutual Regulation ◽  
Summary Statement ◽  
And Migration ◽  
Focal Adhesion Protein

AbstractPlasticity between adhesive and less-adhesive states is important for mammalian cell behaviour. To investigate adhesion plasticity, we have selected a stable isogenic subpopulation of MDA-MB-468 breast carcinoma cells which grows in suspension. These suspension cells are unable to re-adhere to various matrices or to contract three-dimensional collagen lattices. By transcriptome analysis, we identified the focal adhesion protein tensin3 (Tns3) as a determinant of adhesion plasticity. Tns3 is strongly reduced on mRNA and protein level in suspension cells. Furthermore, challenging breast cancer cells transiently with non-adherent conditions markedly reduces Tns3 expression, which is regained upon re-adhesion. Stable knockdown of Tns3 in parental cells results in defective adhesion, spreading and migration. Tns3 knockdown cells display impaired structure and dynamics of focal adhesion complexes as determined by immunostaining. Restoration of Tns3 expression in suspension cells partially rescues adhesion and focal contact composition. Our work identifies Tns3 as a critical focal adhesion component regulated by, and functionally contributing to, the switch between adhesive and non-adhesive states in MDA-MB-468 cancer cells.Summary statementWe identify the cell-matrix adapter protein tensin3 as a determinant of adhesion plasticity, using cancer cells selected for non-adherent growth. Tensin3 expression constitutes a feedback loop controlling adhesion and motility.

Role of Regulatory Oncogenic or Tumor Suppressor miRNAs of PI3K/AKT Signaling Axis in the Pathogenesis of Colorectal Cancer

2019 ◽  
Vol 24 (39) ◽  
pp. 4605-4610 ◽  
Author(s):  
Atena Soleimani ◽  
Farzad Rahmani ◽  
Gordon A. Ferns ◽  
Mikhail Ryzhikov ◽  
Amir Avan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Suppressor ◽  
Current Knowledge ◽  
Akt Signaling ◽  
Tumor Tissues ◽  
Radio Therapy ◽  
Signaling Axis ◽  
Cancer Tumor ◽  
Novel Biomarkers

Colorectal cancer (CRC) is the leading cause of cancer death worldwide and its incidence is increasing. In most patients with CRC, the PI3K/AKT signaling axis is over-activated. Regulatory oncogenic or tumor suppressor microRNAs (miRNAs) for PI3K/AKT signaling regulate cell proliferation, migration, invasion, angiogenesis, as well as resistance to chemo-/radio-therapy in colorectal cancer tumor tissues. Thus, regulatory miRNAs of PI3K/AKT/mTOR signaling represent novel biomarkers for new patient diagnosis and obtaining clinically invaluable information from post-treatment CRC patients for improving therapeutic strategies. This review summarizes the current knowledge of miRNAs’ regulatory roles of PI3K/AKT signaling in CRC pathogenesis.

scholarly journals Hypoxic glioma-derived exosomes promote M2-like macrophage polarization by enhancing autophagy induction

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Jianye Xu ◽  
Jian Zhang ◽  
Zongpu Zhang ◽  
Zijie Gao ◽  
Yanhua Qi ◽  
...  
Keyword(s):  
Macrophage Polarization ◽  
Autophagy Induction ◽  
Antitumor Immunotherapy ◽  
Novel Biomarkers ◽  
And Migration ◽  
Immunosuppressive Microenvironment ◽  
Proliferation And Migration ◽  
Glioma Progression

AbstractExosomes participate in intercellular communication and glioma microenvironment modulation, but the exact mechanisms by which glioma-derived exosomes (GDEs) promote the generation of the immunosuppressive microenvironment are still unclear. Here, we investigated the effects of GDEs on autophagy, the polarization of tumor-associated macrophages (TAMs), and glioma progression. Compared with normoxic glioma-derived exosomes (N-GDEs), hypoxic glioma-derived exosomes (H-GDEs) markedly facilitated autophagy and M2-like macrophage polarization, which subsequently promoted glioma proliferation and migration in vitro and in vivo. Western blot and qRT-PCR analyses indicated that interleukin 6 (IL-6) and miR-155-3p were highly expressed in H-GDEs. Further experiments showed that IL-6 and miR-155-3p induced M2-like macrophage polarization via the IL-6-pSTAT3-miR-155-3p-autophagy-pSTAT3 positive feedback loop, which promotes glioma progression. Our study clarifies a mechanism by which hypoxia and glioma influence autophagy and M2-like macrophage polarization via exosomes, which could advance the formation of the immunosuppressive microenvironment. Our findings suggest that IL-6 and miR-155-3p may be novel biomarkers for diagnosing glioma and that treatments targeting autophagy and the STAT3 pathway may contribute to antitumor immunotherapy.

scholarly journals The roles and prognostic significance of ABI1-TSV-11 expression in patients with left-sided colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu Zhang ◽  
Zhaohui Zhong ◽  
Mei Li ◽  
Jingyi Chen ◽  
Tingru Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
The Cancer Genome Atlas ◽  
Actin Dynamics ◽  
Elevated Expression ◽  
Sw480 Cells ◽  
And Migration

AbstractAbnormally expressed and/or phosphorylated Abelson interactor 1 (ABI1) participates in the metastasis and progression of colorectal cancer (CRC). ABI1 presents as at least 12 transcript variants (TSVs) by mRNA alternative splicing, but it is unknown which of them is involved in CRC metastasis and prognosis. Here, we firstly identified ABI1-TSV-11 as a key TSV affecting the metastasis and prognosis of left-sided colorectal cancer (LsCC) and its elevated expression is related to lymph node metastasis and shorter overall survival (OS) in LsCC by analyzing data from The Cancer Genome Atlas and TSVdb. Secondly, ABI1-TSV-11 overexpression promoted LoVo and SW480 cells adhesion and migration in vitro, and accelerated LoVo and SW480 cells lung metastasis in vivo. Finally, mechanism investigations revealed that ABI1-isoform-11 interacted with epidermal growth factor receptor pathway substrate 8 (ESP8) and regulated actin dynamics to affect LoVo and SW480 cells biological behaviors. Taken together, our data demonstrated that ABI1-TSV-11 plays an oncogenic role in LsCC, it is an independent risk factor of prognosis and may be a potential molecular marker and therapeutic target in LsCC.

scholarly journals Circulating Biomarkers of Colorectal Cancer (CRC)—Their Utility in Diagnosis and Prognosis

2021 ◽  
Vol 10 (11) ◽  
pp. 2391
Author(s):  
Marta Łukaszewicz-Zając ◽  
Barbara Mroczko
Keyword(s):  
Colorectal Cancer ◽  
Inflammatory Mediators ◽  
Colorectal Adenomas ◽  
Global Burden ◽  
Circulating Biomarkers ◽  
Specific Nature ◽  
Diagnosis And Prognosis ◽  
Specific Proteins ◽  
Novel Biomarkers ◽  
Number Of Publications

The global burden of colorectal cancer (CRC) is expected to increase, with 2.2 million new cases and 1.1 million annual deaths by 2030. Therefore, the establishment of novel biomarkers useful in the early diagnosis of CRC is of utmost importance. A number of publications have documented the significance of the overexpression of several specific proteins, such as inflammatory mediators, in CRC progression. However, little is known about the potential utility of these proteins as circulating blood tumor biomarkers of CRC. Therefore, in the present review we report the results of our previous original studies as well as the findings of other authors who investigated whether inflammatory mediators might be used as novel biomarkers in the diagnosis and prognosis of CRC. Our study revealed that among all of the tested proteins, serum M-CSF, CXCL-8, IL-6 and TIMP-1 have the greatest value in the diagnosis and progression of CRC. Serum TIMP-1 is useful in differentiating between CRC and colorectal adenomas, whereas M-CSF and CRP are independent prognostic factors for the survival of patients with CRC. This review confirms the promising significance of these proteins as circulating biomarkers for CRC. However, due to their non-specific nature, further validation of their sensitivity and specificity is required.

scholarly journals Integrated whole transcriptome and small RNA analysis revealed multiple regulatory networks in colorectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hibah Shaath ◽  
Salman M. Toor ◽  
Mohamed Abu Nada ◽  
Eyad Elkord ◽  
Nehad M. Alajez
Keyword(s):  
Colorectal Cancer ◽  
Messenger Rna ◽  
Regulatory Networks ◽  
Potential Interaction ◽  
Therapeutic Interventions ◽  
Signaling Networks ◽  
Protein Coding ◽  
Paired Samples ◽  
And Migration ◽  
Whole Transcriptome

AbstractColorectal cancer (CRC) remains a global disease burden and a leading cause of cancer related deaths worldwide. The identification of aberrantly expressed messenger RNA (mRNA), long non-coding RNA (lncRNA), and microRNA (miRNA), and the resulting molecular interactions and signaling networks is essential for better understanding of CRC, identification of novel diagnostic biomarkers and potential development of therapeutic interventions. Herein, we performed microRNA (miRNA) sequencing on fifteen CRC and their non-tumor adjacent tissues and whole transcriptome RNA-Seq on six paired samples from the same cohort and identified alterations in miRNA, mRNA, and lncRNA expression. Computational analyses using Ingenuity Pathway Analysis (IPA) identified multiple activated signaling networks in CRC, including ERBB2, RABL6, FOXM1, and NFKB networks, while functional annotation highlighted activation of cell proliferation and migration as the hallmark of CRC. IPA in combination with in silico prediction algorithms and experimentally validated databases gave insight into the complex associations and interactions between downregulated miRNAs and upregulated mRNAs in CRC and vice versa. Additionally, potential interaction between differentially expressed lncRNAs such as H19, SNHG5, and GATA2-AS1 with multiple miRNAs has been revealed. Taken together, our data provides thorough analysis of dysregulated protein-coding and non-coding RNAs in CRC highlighting numerous associations and regulatory networks thus providing better understanding of CRC.

scholarly journals The focal adhesion protein Testin modulates KCNE2 potassium channel β subunit activity

Channels ◽  
2021 ◽  
Vol 15 (1) ◽  
pp. 229-238
Author(s):  
Maria Papanikolaou ◽  
Shawn M. Crump ◽  
Geoffrey W. Abbott
Keyword(s):  
Potassium Channel ◽  
Focal Adhesion ◽  
Β Subunit ◽  
Adhesion Protein ◽  
Focal Adhesion Protein
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