▪ Cancer Cell: Linking Oncogenic Signaling to Molecular Structure

2010 ◽  
pp. 56-69 ◽  
Keyword(s):  
Molecular Structure ◽  
Cancer Cell ◽  
Oncogenic Signaling

scholarly journals Oncolytic Virotherapy: The Cancer Cell Side

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 939
Author(s):  
Marcelo Ehrlich ◽  
Eran Bacharach
Keyword(s):  
Viral Replication ◽  
Cancer Cell ◽  
Cell Metabolism ◽  
Tumor Development ◽  
Oncolytic Viruses ◽  
Oncogenic Signaling ◽  
Functional Connection ◽  
Immunity Genes ◽  
Cancer Cell Metabolism ◽  
Editing Process

Cell autonomous immunity genes mediate the multiple stages of anti-viral defenses, including recognition of invading pathogens, inhibition of viral replication, reprogramming of cellular metabolism, programmed-cell-death, paracrine induction of antiviral state, and activation of immunostimulatory inflammation. In tumor development and/or immunotherapy settings, selective pressure applied by the immune system results in tumor immunoediting, a reduction in the immunostimulatory potential of the cancer cell. This editing process comprises the reduced expression and/or function of cell autonomous immunity genes, allowing for immune-evasion of the tumor while concomitantly attenuating anti-viral defenses. Combined with the oncogene-enhanced anabolic nature of cancer-cell metabolism, this attenuation of antiviral defenses contributes to viral replication and to the selectivity of oncolytic viruses (OVs) towards malignant cells. Here, we review the manners by which oncogene-mediated transformation and tumor immunoediting combine to alter the intracellular milieu of tumor cells, for the benefit of OV replication. We also explore the functional connection between oncogenic signaling and epigenetic silencing, and the way by which restriction of such silencing results in immune activation. Together, the picture that emerges is one in which OVs and epigenetic modifiers are part of a growing therapeutic toolbox that employs activation of anti-tumor immunity for cancer therapy.

scholarly journals Inverse PPARβ/δ agonists suppress oncogenic signaling to the ANGPTL4 gene and inhibit cancer cell invasion

Oncogene ◽  
2012 ◽  
Vol 32 (44) ◽  
pp. 5241-5252 ◽  
Author(s):  
T Adhikary ◽  
D T Brandt ◽  
K Kaddatz ◽  
J Stockert ◽  
S Naruhn ◽  
...  
Keyword(s):  
Cancer Cell ◽  
Cell Invasion ◽  
Cancer Cell Invasion ◽  
Oncogenic Signaling

scholarly journals Metabolic reprogramming ensures cancer cell survival despite oncogenic signaling blockade

2017 ◽  
Vol 31 (20) ◽  
pp. 2067-2084 ◽  
Author(s):  
Hui-wen Lue ◽  
Jennifer Podolak ◽  
Kevin Kolahi ◽  
Larry Cheng ◽  
Soumya Rao ◽  
...  
Keyword(s):  
Cell Survival ◽  
Cancer Cell ◽  
Metabolic Reprogramming ◽  
Oncogenic Signaling ◽  
Cancer Cell Survival

scholarly journals Roles of E-cadherin and Noncoding RNAs in the Epithelial–mesenchymal Transition and Progression in Gastric Cancer

2019 ◽  
Vol 20 (12) ◽  
pp. 2870 ◽  
Author(s):  
Irina V. Bure ◽  
Marina V. Nemtsova ◽  
Dmitry V. Zaletaev
Keyword(s):  
Gastric Cancer ◽  
Cancer Cell ◽  
Rho Gtpase ◽  
Epithelial Mesenchymal Transition ◽  
Metastatic Cancer ◽  
Noncoding Rnas ◽  
Oncogenic Signaling ◽  
Control Of Gene Expression ◽  
Mesenchymal Transition ◽  
E Cadherin

The epithelial–mesenchymal transition (EMT) is thought to be at the root of invasive and metastatic cancer cell spreading. E-cadherin is an important player in this process, which forms the structures that establish and maintain cell–cell interactions. A partial or complete loss of E-cadherin expression in the EMT is presumably mediated by mechanisms that block the expression of E-cadherin regulators and involve the E-cadherin-associated transcription factors. The protein is involved in several oncogenic signaling pathways, such as the Wnt/β-catenin, Rho GTPase, and EGF/EGFR, whereby it plays a role in many tumors, including gastric cancer. Such noncoding transcripts as microRNAs and long noncoding RNAs—critical components of epigenetic control of gene expression in carcinogenesis—contribute to regulation of the E-cadherin function by acting directly or through numerous factors controlling transcription of its gene, and thus affecting not only cancer cell proliferation and metastasis, but also the EMT. This review focuses on the role of E-cadherin and the non-coding RNAs-mediated mechanisms of its expressional control in the EMT during stomach carcinogenesis.

Inhibition of cMET in an experimental model of pancreatic cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 185-185
Author(s):  
Sven A. Lang ◽  
Franziska Brandes ◽  
Edward K. Geissler
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Oncogenic Signaling

185 Background: In human pancreatic cancer, expression of cMET is associated with poor survival. So far, activation/expression of cMET by hepatocyte growth factor (HGF) has been shown to induce proliferation and motility in cancer cells. Therefore, we hypothesized that inhibition of cMET in human pancreatic cancer cell lines impairs oncogenic signaling and tumor growth. Methods: Pancreatic cancer cell lines (HPAF-II, MiaPaCa2, L3.6pl, BxPC3, Panc02) and the cMET inhibitor INC280 (Novartis Oncology, Basel) were used. MiaPaCa2 and L3.6pl pancreatic cancer cells were grown with gemcitabine up to 500 and 250 nM, respectively (then called MiaPaCa2(G500) and L3.6pl(G250)). MTT and Boyden Chamber assays were used to determine effects of INC280 on growth and motility of cells in vitro. Expression of growth factor receptors, activation of signaling intermediates and expression of transcription factors were assessed by Western blotting. Finally, in vitro results were validated in an orthotopic tumor model using L3.6pl pancreatic cancer cell line. Results: All pancreatic cancer cell lines showed expression of cMET. In vitro treatment of cancer cells with INC280 led to a minor, dose-dependent inhibition of growth even when cells were supplemented with HGF. In contrast, migration assays showed a significant reduction of cancer cell motility upon INC280 when cells were stimulated with HGF (P<0.05). Regarding oncogenic signaling, INC280 led to inhibition of HGF-induced phosphorylation of AKT, ERK and FAK. In addition, c-Myc expression was diminished in cancer cells. Interestingly, gemcitabine resistant cell line MiaPaCa2(G500) showed higher cMET expression levels compared to the normal MiaPaCa2. Stimulation of MiaPaCa2(G500) with HGF led to strong induction of oncogenic signaling and tumor cell motility, an effect that was significantly diminished by INC280. Moreover, results from in vivo experiments show that therapy with INC280 (10 mg/kg/d) significantly reduces tumor growth as determined by final tumor weight (P<0.05). Conclusions: In pancreatic cancer cell lines, targeting cMET with INC280 abrogates oncogenic signaling in vitro and impairs tumor growth in vivo. Therefore, the concept of cMET inhibition warrants further preclinical evaluation.

scholarly journals Rewiring of Cancer Cell Metabolism by Mitochondrial VDAC1 Depletion Results in Time-Dependent Tumor Reprogramming: Glioblastoma as a Proof of Concept

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1330 ◽  
Author(s):  
Arif ◽  
Stern ◽  
Pittala ◽  
Chalifa-Caspi ◽  
Shoshan-Barmatz
Keyword(s):  
Cancer Cell ◽  
Cell Metabolism ◽  
Anion Channel ◽  
Translocator Protein ◽  
Global Changes ◽  
Voltage Dependent Anion Channel ◽  
Oncogenic Signaling ◽  
Neuronal Markers ◽  
Long Period

Reprograming of the metabolism of cancer cells is an event recognized as a hallmark of the disease. The mitochondrial gatekeeper, voltage-dependent anion channel 1 (VDAC1), mediates transport of metabolites and ions in and out of mitochondria, and is involved in mitochondria-mediated apoptosis. Here, we compared the effects of reducing hVDAC1 expression in a glioblastoma xenograft using human-specific si-RNA (si-hVDAC1) for a short (19 days) and a long term (40 days). Tumors underwent reprograming, reflected in rewired metabolism, eradication of cancer stem cells (CSCs) and differentiation. Short- and long-term treatments of the tumors with si-hVDAC1 similarly reduced the expression of metabolism-related enzymes, and translocator protein (TSPO) and CSCs markers. In contrast, differentiation into cells expressing astrocyte or neuronal markers was noted only after a long period during which the tumor cells were hVDAC1-depleted. This suggests that tumor cell differentiation is a prolonged process that precedes metabolic reprograming and the “disappearance” of CSCs. Tumor proteomics analysis revealing global changes in the expression levels of proteins associated with signaling, synthesis and degradation of proteins, DNA structure and replication and epigenetic changes, all of which were highly altered after a long period of si-hVDAC1 tumor treatment. The depletion of hVDAC1 greatly reduced the levels of the multifunctional translocator protein TSPO, which is overexpressed in both the mitochondria and the nucleus of the tumor. The results thus show that VDAC1 depletion-mediated cancer cell metabolic reprograming involves a chain of events occurring in a sequential manner leading to a reversal of the unique properties of the tumor, indicative of the interplay between metabolism and oncogenic signaling networks.

scholarly journals WNT Signaling: an Emerging Mediator of Cancer Cell Metabolism?

2014 ◽  
Vol 35 (1) ◽  
pp. 2-10 ◽  
Author(s):  
Victoria Sherwood
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Cancer Cell ◽  
Cancer Metabolism ◽  
Cell Metabolism ◽  
Critical Role ◽  
Oncogenic Signaling ◽  
Cancer Cell Metabolism ◽  
Oncogenic Signaling Pathways

WNT signaling was discovered in tumor models and has been recognized as a regulator of cancer development and progression for over 3 decades. Recent work has highlighted a critical role for WNT signaling in the metabolic homeostasis of mammals, where its misregulation has been heavily implicated in diabetes. While the majority of WNT metabolism research has focused on nontransformed tissues, the role of WNT in cancer metabolism remains underinvestigated. Cancer is also a metabolic disease where oncogenic signaling pathways regulate energy production and macromolecular synthesis to fuel rapidly proliferating tumors. This review highlights the emerging evidence for WNT signaling in the reprogramming of cancer cell metabolism and examines the role of these signaling pathways as mediators of tumor bioenergetics.

scholarly journals Effects of Intestinal Microbial–Elaborated Butyrate on Oncogenic Signaling Pathways

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1026 ◽  
Author(s):  
Jiezhong Chen ◽  
Kong-Nan Zhao ◽  
Luis Vitetta
Keyword(s):  
Cell Differentiation ◽  
Cancer Prevention ◽  
Signaling Pathways ◽  
Cancer Cell ◽  
Short Chain Fatty Acids ◽  
T Regulatory Cell ◽  
Oncogenic Signaling ◽  
Anti Cancer ◽  
Prevention And Treatment ◽  
Oncogenic Signaling Pathways

The intestinal microbiota is well known to have multiple benefits on human health, including cancer prevention and treatment. The effects are partially mediated by microbiota-produced short chain fatty acids (SCFAs) such as butyrate, propionate and acetate. The anti-cancer effect of butyrate has been demonstrated in cancer cell cultures and animal models of cancer. Butyrate, as a signaling molecule, has effects on multiple signaling pathways. The most studied effect is its inhibition on histone deacetylase (HDAC), which leads to alterations of several important oncogenic signaling pathways such as JAK2/STAT3, VEGF. Butyrate can interfere with both mitochondrial apoptotic and extrinsic apoptotic pathways. In addition, butyrate also reduces gut inflammation by promoting T-regulatory cell differentiation with decreased activities of the NF-κB and STAT3 pathways. Through PKC and Wnt pathways, butyrate increases cancer cell differentiation. Furthermore, butyrate regulates oncogenic signaling molecules through microRNAs and methylation. Therefore, butyrate has the potential to be incorporated into cancer prevention and treatment regimens. In this review we summarize recent progress in butyrate research and discuss the future development of butyrate as an anti-cancer agent with emphasis on its effects on oncogenic signaling pathways. The low bioavailability of butyrate is a problem, which precludes clinical application. The disadvantage of butyrate for medicinal applications may be overcome by several approaches including nano-delivery, analogue development and combination use with other anti-cancer agents or phytochemicals.

Sign in / Sign up

Export Citation Format

Share Document