Cellular Migration Ability Is Modulated by Extracellular Purines in Ovarian Carcinoma SKOV-3 Cells

2017 ◽  
Vol 118 (12) ◽  
pp. 4468-4478 ◽  
Author(s):  
A.S. Martínez-Ramírez ◽  
M. Díaz-Muñoz ◽  
A.M. Battastini ◽  
A. Campos-Contreras ◽  
A. Olvera ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Cellular Migration ◽  
Migration Ability ◽  
Extracellular Purines

Transgelin as a therapeutic target to prevent hypoxic pulmonary hypertension

2014 ◽  
Vol 306 (6) ◽  
pp. L574-L583 ◽  
Author(s):  
Ruifeng Zhang ◽  
Liuhong Shi ◽  
Lin Zhou ◽  
Gensheng Zhang ◽  
Xiaohong Wu ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Lentiviral Vector ◽  
Hypoxia Inducible Factor ◽  
Systolic Pressure ◽  
Cellular Migration ◽  
Regulation Mechanism ◽  
Migration Ability ◽  
Pulmonary Vessel ◽  
Hypoxic Pulmonary Hypertension

We previously observed that transgelin was preferentially expressed in human pulmonary arterial smooth muscle cells (PAMSCs) under hypoxia and that the upregulation of transgelin was independent of hypoxia-inducible factor 1α (HIF-1α). Reduced transgelin expression was accompanied by significantly impaired migration ability in vitro. However, the regulation mechanism of transgelin and its function in preventing hypoxic pulmonary hypertension (HPH) was unclear. In the present study, RNA interference with hypoxia-inducible factor 2α (HIF-2α) was employed in human PASMCs. Transgelin expression was diminished in HIF-2α-siRNA-treated cells at both the mRNA and protein levels under hypoxia. However, HIF-2α did not transactivate the transgelin promoter directly. TGF-β1 concentration in human PASMCs culture medium was higher under hypoxia, and the accumulated TGF-β1 under hypoxia was regulated by HIF-2α. Furthermore, luciferase and chromatin immunoprecipitation assays indicated that TGF-β1/Smad3 could bind to the transgelin promoter, resulting in increased transgelin expression. In addition to nonintact cellular migration, inhibition of transgelin expression resulted in impaired proliferation in vitro under hypoxia. A lentiviral vector used to inhibit transgelin expression was constructed and intratracheally instilled in rats 3 wk prior to hypoxia treatment. Our final results indicated that inhibition of transgelin expression locally could attenuate increased right ventricular systolic pressure and its associated cardiac and pulmonary vessel remodeling under hypoxia. Our findings indicate that HIF-2α upregulates transgelin indirectly and that accumulated TGF-β1 is a mediator in the upregulation of transgelin by HIF-2α under hypoxia. Inhibition of transgelin expression locally could prevent HPH and pulmonary vascular remodeling in vivo.

scholarly journals SH3BGRL3 binds to myosin 1c in a calcium dependent manner and modulates migration in the MDA-MB-231 cell line

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Filippo Di Pisa ◽  
Elisa Pesenti ◽  
Maria Bono ◽  
Andrea N. Mazzarello ◽  
Cinzia Bernardi ◽  
...  
Keyword(s):  
Cell Migration ◽  
Plasma Membranes ◽  
Neck Region ◽  
Cellular Migration ◽  
Regulation Mechanism ◽  
Dependent Manner ◽  
Migration Ability ◽  
Calcium Dependent ◽  
Egfr Family ◽  
Cytoskeleton Dynamics

Abstract Background The human SH3 domain Binding Glutamic acid Rich Like 3 (SH3BGRL3) gene is highly conserved in phylogeny and widely expressed in human tissues. However, its function is largely undetermined. The protein was found to be overexpressed in several tumors, and recent work suggested a possible relationship with EGFR family members. We aimed at further highlighting on these issues and investigated SH3BGRL3 molecular interactions and its role in cellular migration ability. Results We first engineered the ErbB2-overexpressing SKBR3 cells to express exogenous SH3BGRL3, as well as wild type Myo1c or different deletion mutants. Confocal microscopy analysis indicated that SH3BGRL3 co-localized with Myo1c and ErbB2 at plasma membranes. However, co-immunoprecipitation assays and mass spectrometry demonstrated that SH3BGRL3 did not directly bind ErbB2, but specifically recognized Myo1c, on its IQ-bearing neck region. Importantly, the interaction with Myo1c was Ca2+-dependent. A role for SH3BGRL3 in cell migration was also assessed, as RNA interference of SH3BGRL3 in MDA-MB-231 cells, used as a classical migration model, remarkably impaired the migration ability of these cells. On the other side, its over-expression increased cell motility. Conclusion The results of this study provide insights for the formulation of novel hypotheses on the putative role of SH3BGRL3 protein in the regulation of myosin-cytoskeleton dialog and in cell migration. It could be envisaged the SH3BGRL3-Myo1c interaction as a regulation mechanism for cytoskeleton dynamics. It is well known that, at low Ca2+ concentrations, the IQ domains of Myo1c are bound by calmodulin. Here we found that binding of Myo1c to SH3BGRL3 requires instead the presence of Ca2+. Thus, it could be hypothesized that Myo1c conformation may be modulated by Ca2+-driven mechanisms that involve alternative binding by calmodulin or SH3BGRL3, for the regulation of cytoskeletal activity.

scholarly journals Lactotransferrin Downregulation Drives the Metastatic Progression in Clear Cell Renal Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 847
Author(s):  
I-Jen Chiu ◽  
Yung-Ho Hsu ◽  
Jeng-Shou Chang ◽  
Jou-Chun Yang ◽  
Hui-Wen Chiu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Metastatic Potential ◽  
Gene Set Enrichment Analysis ◽  
Cellular Migration ◽  
Metastatic Progression ◽  
Migration Ability ◽  
Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is the main type of RCC, which is the most common type of malignant kidney tumor in adults. A subpopulation (>30%) of ccRCC patients develop metastasis; however, the molecular mechanism remains largely unknown. Here, we found that LTF, the gene encoding lactotransferrin, is dramatically downregulated in primary tumors compared to normal tissues derived from ccRCC patients deposited in The Cancer Genome Atlas (TCGA) database and is a favorable prognostic marker. Moreover, LTF downregulation appears to be more dominant in metastatic ccRCC. LTF overexpression suppresses migration ability in A498 ccRCC cells with high metastatic potential, whereas LTF knockdown fosters cellular migration in poorly metastatic ccRCC cells. Gene set enrichment analysis demonstrated that LTF expression inversely correlates with the progression of epithelial-mesenchymal transition (EMT) in ccRCC, which was further confirmed by RT-PCR experiments. Therapeutically, the administration of recombinant LTF protein significantly suppresses the cell migration ability and lung metastatic potential of ACHN cells, as well as LTF-silenced A498 cells. The gene knockdown of lipoprotein receptor-related protein 1 (LRP1) robustly blocked recombinant LTF protein-induced inhibition of cellular migration and gene expression of EMT markers in ACHN cells. LTF downregulation and LRP1 upregulation combined predicted a poor overall survival rate in ccRCC patients compared to that with either factor alone. Our findings uncover a new mechanism by which LTF may interact with LRP1 to inhibit metastatic progression in ccRCC and also reveal the therapeutic value of recombinant LTF protein in treating metastatic ccRCC.

scholarly journals Motility and Mechanical Properties of Dendritic Cells Deteriorated by Extracellular Acidosis

Inflammation ◽  
2020 ◽  
Author(s):  
Lu Tong ◽  
Ping Yue ◽  
Yingying Yang ◽  
Jin Huang ◽  
Zhu Zeng ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Dendritic Cells ◽  
Cell Structure ◽  
Osmotic Fragility ◽  
Cellular Migration ◽  
Migration Ability ◽  
Actin Organization ◽  
Extracellular Acidosis ◽  
Proliferation Capacity ◽  
And Function

Abstract Dendritic cells (DCs) are the most powerful antigen-presenting cells known to date and play an important role in initiating and amplifying both innate and adaptive immune responses. Extracellular acidosis is an important hallmark of a variety of inflammatory processes and solid tumors. However, few studies have focused on the effect of extracellular acidosis on DCs and their functions. Cellular mechanical properties reflect the relationship between cell structure and function, including cytoskeleton (especially F-actin organization), membrane negative charges, membrane fluidity, and osmotic fragility. The study investigated the effects of extracellular acidosis on the DCs functions from the perspective of cellular migration and mechanical properties. The results showed that migration ability, F-actin contents, and membrane negative charges of DCs were reduced by extracellular acidosis no matter whether LPS stimulated its maturation or not. And these functions could not return to normal after removing acidic microenvironment, which revealed that the function impairment induced by extracellular acidosis might be irreversible. In addition, the proliferation capacity of stimulated allogeneic T cells was impaired by extracellular acidosis. Our results suggest extracellular acidosis may play an immunosuppressive role in DCs-mediated immune process.

scholarly journals Lactotransferrin Downregulation Serves as a Potential Predictor for the Therapeutic Effectiveness of mTOR Inhibitors in the Metastatic Clear Cell Renal Cell Carcinoma without PTEN Mutation

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1896
Author(s):  
Jing-Quan Zheng ◽  
Che-Hsuan Lin ◽  
Hsun-Hua Lee ◽  
Wen-Ke Wang ◽  
Yiu-Shun Tong ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Clear Cell ◽  
Progression Free Survival ◽  
Mtor Inhibitors ◽  
Cellular Migration ◽  
Therapeutic Effectiveness ◽  
Migration Ability ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival ◽  
Gene Set

Approximately 30% of clear cell renal cell carcinoma (ccRCC) patients develop metastatic spread at the first diagnosis. Therefore, identifying a useful biomarker to predict ccRCC metastasis or therapeutic effectiveness in ccRCC patients is urgently needed. Previously, we demonstrated that lactotransferrin (LTF) downregulation enhanced the metastatic potential of ccRCC. Here, we show that LTF expression conversely associates with the mTORC1 activity as simulated by gene set enrichment analysis (GSEA). Moreover, Western blot analyses revealed that the LTF knockdown promoted, but the inclusion of recombinant human LTF protein suppressed, the phosphorylation of Akt/mTOR proteins in the detected ccRCC cells. Kaplan–Meier analyses demonstrated that the signature of combining an upregulated mTORC1 activity with a downregulated LTF expression referred to a worse overall and progression-free survival probabilities and associated with distant cancer metastasis in TCGA ccRCC patients. Furthermore, we found that the LTF-suppressed Akt/mTOR activation triggered an increased formation of autophagy in the highly metastatic ccRCC cells. The addition of autophagy inhibitor 3-methyadenine restored the LTF-suppressed cellular migration ability of highly metastatic ccRCC cells. Receiver operating characteristic (ROC) analyses showed that the expression of the LTF and MTORC1 gene set, not the autophagy gene set, could be the useful biomarkers to predict 5-year overall survival rate and cancer progression in ccRCC patients. Significantly, the signature of combining mTORC1 upregulation and LTF downregulation was shown as an independent prognostic factor in a multivariate analysis under the progression-free survival condition using the TCGA ccRCC database. Finally, the treatment with mTOR inhibitor rapamycin predominantly reduced the formation of autophagy and ultimately mitigated the cellular migration ability of ccRCC cells with LTF knockdown. Our findings suggest that LTF downregulation is a biomarker for guiding the use of mTOR inhibitors to combat metastatic ccRCC in the clinic.

scholarly journals Tumor-suppressor miRNA-27b-5p regulates the growth and metastatic behaviors of ovarian carcinoma cells by targeting CXCL1

2020 ◽  
Author(s):  
Shan Yong Qin ◽  
Min Wei Liu
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Carcinoma ◽  
Ovarian Cancer Patient ◽  
Carcinoma Cell ◽  
Carcinoma Cells ◽  
Skov3 Cell ◽  
Migration Ability ◽  
Ovarian Carcinoma Cells ◽  
A2780 Cell ◽  
Chemokine Ligand

Abstract MicroRNAs (miRNAs) play crucial functions in the progression of ovarian cancer. MiR-27b has been identified as cancer-associated miRNA. Nevertheless, the expression profile of microRNA-27b-5p (miR-27b-5p) and its functions in ovarian cancer are unexplored. Here, we demonstrated that miR-27b-5p was downregulated in ovarian carcinoma cells and clinical specimens. Higher expression of miR-27b-5p was allied to an unfavorable overall survival in ovarian cancer patient. Upregulation of miR-27b-5p decreased the viability, migration ability and invasion capacity of SKOV3 and A2780 cell. MiR-27b-5p also inhibited the growth of SKOV3 cell in nude mice. Additionally, we verified that C-X-C motif chemokine ligand 1 (CXCL1) was a target of miR-27b-5p in ovarian carcinoma cell. Restoring the expression of CXCL1 abolished the inhibitory impacts of miR-27b-5p in ovarian cancer carcinoma cell. This research revealed that miR-27b-5p restrained the progression of ovarian carcinoma possibly via targeting CXCL1.

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