scholarly journals Roles of Farnesyl-Diphosphate Farnesyltransferase 1 in Tumour and Tumour Microenvironments

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2352
Author(s):  
Nguyen Thi Ha ◽  
Chang Hoon Lee
Keyword(s):  
Cell Proliferation ◽  
Cancer Treatment ◽  
Critical Role ◽  
Anticancer Therapy ◽  
Squalene Synthase ◽  
Farnesyl Diphosphate ◽  
Metabolic Reprogramming ◽  
Farnesyl Pyrophosphate ◽  
Hallmarks Of Cancer ◽  
Proliferation And Invasion

Farnesyl-diphosphate farnesyltransferase 1 (FDFT1, squalene synthase), a membrane-associated enzyme, synthesizes squalene via condensation of two molecules of farnesyl pyrophosphate. Accumulating evidence has noted that FDFT1 plays a critical role in cancer, particularly in metabolic reprogramming, cell proliferation, and invasion. Based on these advances in our knowledge, FDFT1 could be a potential target for cancer treatment. This review focuses on the contribution of FDFT1 to the hallmarks of cancer, and further, we discuss the applicability of FDFT1 as a cancer prognostic marker and target for anticancer therapy.

scholarly journals CD206+ tumor-associated macrophages promote proliferation and invasion in oral squamous cell carcinoma via EGF production

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
A. S. M. Rafiul Haque ◽  
Masafumi Moriyama ◽  
Keigo Kubota ◽  
Noriko Ishiguro ◽  
Mizuki Sakamoto ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Conditioned Medium ◽  
Squamous Cell ◽  
Critical Role ◽  
Tumor Associated Macrophages ◽  
Clinical Prognosis ◽  
Proliferation And Invasion

Abstract Tumor-associated macrophages (TAMs) promote tumor progression and inhibit anti-tumor immune response by producing various mediators and preferentially express CD163, CD204, and CD206. However, the role of these TAM subsets in oral squamous cell carcinoma (OSCC) remains unclear. Here we investigated the expression and function of TAM subsets in OSCC, especially in cancer cell proliferation. Biopsy sample from 44 patients with OSCC were examined for the expression of TAM markers and EGF by immunohistochemistry. EGF production of TAM subsets isolated from OSCC patients was assessed by flow cytometry. We also examined the effect of conditioned medium from TAM subsets on the proliferation of OSCC cells. CD163+ cells were detected diffusely all over the tumor and connective tissue area, while CD204+ and CD206+ cells were mainly detected in/around the tumors. Flow cytometric analysis found that CD206+ TAMs strongly produced EGF compared with CD163+ and CD204+ TAMs. Cell proliferation and invasion of OSCC cells cultured with conditioned medium of CD206+ TAMs were strongly enhanced and inhibited by anti-EGFR. The number of CD206+ TAMs positively correlated with worse clinical prognosis. Our results revealed differences in localization and EGF production among these TAM subsets. CD206+ TAMs might play a critical role in the proliferation of OSCC via EGF production.

scholarly journals LncRNA NONHSAT114552 Sponges miR-320d to Promote Proliferation and Invasion of Chordoma Through Upregulating NRP1

2021 ◽  
Vol 12 ◽  
Author(s):  
Kai Zhang ◽  
Zixiang Liu ◽  
Yingchuang Tang ◽  
Xiaofeng Shao ◽  
Xi Hua ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Clinical Prognosis ◽  
Kaplan Meier ◽  
Neuropilin 1 ◽  
Competitive Endogenous Rnas ◽  
Proliferation And Invasion

Chordoma is a relatively rare malignant bone tumor with high local recurrence. To date, the mechanism remains unclear. lncRNAs play a pivotal role in tumorigenesis by acting as competitive endogenous RNAs of microRNAs. However, the biological role of lncRNA is still unclear in chordoma. In this research, our aim is to investigate the roles and regulation mechanisms of lncRNA NONHSAT114552 in chordoma development. The expression level of NONHSAT114552 and miR-320d in chordoma tissues was determined by qRT-PCR. Meantime, the correlation between NONHSAT114552 and clinical prognosis was also studied. Bioinformatics analysis and luciferase reporter assays were used to verify the relationship between NONHSAT114552 and miR-320d, and between miR-320d and Neuropilin 1 (NRP1). In addition, effects of NONHSAT114552 on chordoma cells (U-CH1 and U-CH2) proliferation and invasion and its regulation on miR-320d were also evaluated. Furthermore, the influences of NONHSAT114552/miR-320d/NRP1 axis on chordoma tumorigenesis were investigated in vivo. NONHSAT114552 was overexpressed while miR-320d was down-regulated in chordoma tissue compared to fetal nucleus pulposus. Kaplan-Meier survival analysis showed that NONHSAT114552 overexpression was associated with patients’ poor prognosis. Knockdown of NONHSAT114552 significantly suppressed chordoma cell proliferation and invasion. In vitro studies confirmed that NONHSAT114552 acted as ceRNA to regulate NRP1 by directly sponging miR-320d, thus facilitating chordoma cell proliferation and invasion. In vivo study demonstrated that NONHSAT114552 moderated chordoma growth by sponging miR-320d to regulating NRP1. Our findings indicate that lncRNA NONHSAT114552 exhibits a critical role in the tumorigenesis and development of chordoma and it may become one potential prognostic marker and therapeutic target for this disease. .

TAMI-45. MICROGLIAL CYTOKINES INDUCE INVASIVENESS AND PROLIFERATION THROUGH PYK2 AND FAK ACTIVATION IN HUMAN GLIOBLASTOMA CELL

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi207-vi208
Author(s):  
Rebeca Nunez ◽  
Miguel Mayol-Del Valle ◽  
Luis Almodovar ◽  
Lilia Kucheryavykh
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Glioma Cell ◽  
Expression Patterns ◽  
Critical Role ◽  
Cell Fraction ◽  
Glioma Invasion ◽  
Glioma Cell Proliferation ◽  
Proliferation And Invasion

Abstract Glioblastoma (GBM) is the most aggressive and highly invasive primary brain tumor in adults. Evidence suggests that microglia create a microenvironment favoring glioma invasion and proliferation. Indeed, previous reports indicate the involvement of focal adhesion kinase (FAK) signaling cascades in glioma cell proliferation. Besides, studies from our laboratory support a critical role of Pyk2, a relative of FAK, in glioma invasion by tumor-infiltrating microglia. However, the microglial-released factors modulating Pyk2 and FAK signaling pathways are unknown. In this study, 20 human GBM specimens were evaluated to identify the cytokine expression patterns in purified microglia and FAK and Pyk2 phosphorylation in glioma cell fraction by RT-PCR and western blot. A Pierson correlation test demonstrated a high correlation (0.8-1.0) of gene expression for PDGFα, PDGFβ, SDF-1α, IL-6, IL-8, and EGF in percoll-purified microglia, and pPyk2(Y579/580) and pFAK(Y925) levels in glioma cell fraction. The role of cytokines in cell invasion and proliferation by Pyk2/FAK activation was further investigated in primary cell lines from three patients. Thirty percent up-regulation of pPyk2 and pFAK was detected in glioma cells treated (2 hrs.) with microglia conditioned media (MCM) compared to control cells. siPyk2 or siFAK knockdown identified IL-6 (100 μM) and EGF (1 μM) as key factors of Pyk2- and FAK-dependent activation in all glioma cell lines. Similar results with siPyk2 or siFAK were observed for matrix degradation, invadopodia formation, cell viability, and mitosis. Indeed, Tocilizumab (IL-6R blocker, 100 ng/mL) and Gefitinib (EGFR blocker, 1 μM) reversed the effect of MCM on glioma cell proliferation and invasion in all cell lines evaluated. These findings support a pivotal role of Pyk2 and FAK in enhancing proliferation and invasion of glioma tumors through IL-6 and EGF-dependent pathways. The latter could be of clinical relevance for new therapeutic developments in GBM patients.

scholarly journals Linking Metabolic Reprogramming, Plasticity and Tumor Progression

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 762
Author(s):  
Oleg Shuvalov ◽  
Alexandra Daks ◽  
Olga Fedorova ◽  
Alexey Petukhov ◽  
Nickolai Barlev
Keyword(s):  
Cancer Cells ◽  
Metabolic Pathways ◽  
Anticancer Therapy ◽  
Metabolic Reprogramming ◽  
Hallmarks Of Cancer ◽  
Primary Tumors ◽  
Molecular Features ◽  
Altered Metabolism ◽  
Key Features ◽  
Tissue Of Origin

The specific molecular features of cancer cells that distinguish them from the normal ones are denoted as “hallmarks of cancer”. One of the critical hallmarks of cancer is an altered metabolism which provides tumor cells with energy and structural resources necessary for rapid proliferation. The key feature of a cancer-reprogrammed metabolism is its plasticity, allowing cancer cells to better adapt to various conditions and to oppose different therapies. Furthermore, the alterations of metabolic pathways in malignant cells are heterogeneous and are defined by several factors including the tissue of origin, driving mutations, and microenvironment. In the present review, we discuss the key features of metabolic reprogramming and plasticity associated with different stages of tumor, from primary tumors to metastases. We also provide evidence of the successful usage of metabolic drugs in anticancer therapy. Finally, we highlight new promising targets for the development of new metabolic drugs.

Clinical Significance of miR-575 in Ovarian Cancer and Its Effect on Ovarian Cancer Cells

2020 ◽  
Vol 12 (9) ◽  
pp. 1087-1094
Author(s):  
Jie Wang ◽  
Weixin Zhou ◽  
Xilun Gan ◽  
Jianbo Yang
Keyword(s):  
Ovarian Cancer ◽  
Cell Proliferation ◽  
Critical Role ◽  
Protein Detection ◽  
Ovarian Cancer Cells ◽  
Control Group ◽  
Pten Protein ◽  
Apoptosis Protein ◽  
The Impact ◽  
Proliferation And Invasion

Ovarian cancer (OC) is a common form of gynecological cancer that increases in incidence annually, seriously threatening the health and safety of patients. The critical role of miR-575 in multiple neoplastic diseases has already been well established. We suspected that miRNA-575 may be strongly associated with the occurrence of OC and may be the key to OC diagnosis and treatment in the future. To test this hypothesis, we selected 68 OC patients (research group, or RG) who were admitted to our hospital and 60 concurrent healthy controls (control group, or CG) as the study participants. Human OC cell lines A2780, OVCAR-3, and SK-OV-3, and human normal ovarian epithelial cells IOSE80 were used in this study. Nanoparticle-assisted polymerase chain reaction (Nano-PCR), was used to identify miRNA-575 expression and its diagnostic implications in OC. miRNA-575 expression in OC cells and its influence on OC cell biological behaviors were investigated, and the correlation between miR-575 and the phosphatase and tensin homolog (PTEN) was discussed. The results revealed a highly expressed miRNA-575 in OC. Detection of biological behaviors was conducted after transfection of miRNA-575 into OC cells. Cell proliferation and invasion in the mimics-miRNA-575 group was statistically enhanced compared to the negative control (NC) and ininhibition-miRNA-575 groups, and the apoptosis and apoptosis protein count significantly declined (P < 0.05). Subsequently, PTEN was observed to present a lower expression in OC cells. Online target gene analysis website (http://www.targetscan.org/vert_72/) identified the related sites that could bind miR-575 and PTEN. PTEN protein detection in the mimics-miR-575, ininhibition-miR-575, and NC groups showed that the PTEN protein expression in the mimics-miR-575 group was reduced in comparison with that of the other groups, while that for ininhibition-miR-575 was elevated compared to that of the NC group (P < 0.05). Therefore, we came to the conclusion that a high expression of miR-575 can bolster OC cell proliferation and invasion and inhibit apoptosis, while the impact of miR-575 on OC cells may be achieved via targeting the PTEN protein. miR-575 presents important clinical applications in OC diagnosis as an underlying therapeutic target of OC and is a major breakthrough toward future OC research.

NOB1: A Potential Biomarker or Target in Cancer

2019 ◽  
Vol 20 (10) ◽  
pp. 1081-1089
Author(s):  
Weiwei Ke ◽  
Zaiming Lu ◽  
Xiangxuan Zhao
Keyword(s):  
Cancer Treatment ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Binding Protein ◽  
Tumor Development ◽  
Anticancer Therapy ◽  
Research Progress ◽  
Normal Tissues ◽  
Potential Biomarker

Human NIN1/RPN12 binding protein 1 homolog (NOB1), an RNA binding protein, is expressed ubiquitously in normal tissues such as the lung, liver, and spleen. Its core physiological function is to regulate protease activities and participate in maintaining RNA metabolism and stability. NOB1 is overexpressed in a variety of cancers, including pancreatic cancer, non-small cell lung cancer, ovarian cancer, prostate carcinoma, osteosarcoma, papillary thyroid carcinoma, colorectal cancer, and glioma. Although existing data indicate that NOB1 overexpression is associated with cancer growth, invasion, and poor prognosis, the molecular mechanisms behind these effects and its exact roles remain unclear. Several studies have confirmed that NOB1 is clinically relevant in different cancers, and further research at the molecular level will help evaluate the role of NOB1 in tumors. NOB1 has become an attractive target in anticancer therapy because it is overexpressed in many cancers and mediates different stages of tumor development. Elucidating the role of NOB1 in different signaling pathways as a potential cancer treatment will provide new ideas for existing cancer treatment methods. This review summarizes the research progress made into NOB1 in cancer in the past decade; this information provides valuable clues and theoretical guidance for future anticancer therapy by targeting NOB1.

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