Role of the cytoskeleton in restoration of normal morphology of transformed cells in culture

1985 ◽  
Vol 100 (1) ◽  
pp. 941-944
Author(s):  
L. A. Lyass
Keyword(s):  
Transformed Cells ◽  
Normal Morphology ◽  
Cells In Culture

Role of pro-opiomelanocortin-derived peptides in the regulation of steroid production by human fetal adrenal cells in culture

1983 ◽  
Vol 97 (3) ◽  
pp. 357-367 ◽  
Author(s):  
Andrew Baird ◽  
K. W. Kan ◽  
Samuel Solomon
Keyword(s):  
Peptide Hormones ◽  
The Other ◽  
Dehydroepiandrosterone Sulphate ◽  
Steroid Production ◽  
Adrenal Cells ◽  
The Third ◽  
Cells In Culture

Synthetic (1–39)ACTH, (1–24)ACTH, (18–39)ACTH, α-MSH, met-enkephalin and α-, βand γ-endorphin were tested for their ability to stimulate steroidogenesis by human fetal adrenal cells in culture. Adrenal cells were incubated with peptide hormones for two periods of 24 h. On the third day of the experiment the cells were incubated with progesterone (4 μg/2 ml) for 8 h. At the doses tested only (1–39)ACTH, (1–24)ACTH and α-MSH stimulated steroidogenesis. None of the other peptides had any corticotrophic effect on the formation of cortisol, corticosterone or dehydroepiandrosterone sulphate (DHAS). At the highest doses tested, α-MSH (100 μg/2 ml) had a corticotrophic effect that was not different from that obtained with 20 ng (1–39)ACTH or (1–24)ACTH. At the lower doses (0·2–2 μg/2 ml), α-MSH stimulated the formation of DHAS (P<0·01) without stimulating the formation of cortisol.

scholarly journals Signaling Pathways Regulating TC21-induced Tumorigenesis

2007 ◽  
Vol 282 (38) ◽  
pp. 27713-27720 ◽  
Author(s):  
Mete Erdogan ◽  
Ambra Pozzi ◽  
Neil Bhowmick ◽  
Harold L Moses ◽  
Roy Zent
Keyword(s):  
P38 Mapk ◽  
Cancer Progression ◽  
Transforming Growth Factor ◽  
Cellular Transformation ◽  
Tumor Formation ◽  
Transformed Cells ◽  
Growth Inhibitory ◽  
Phosphoinositide 3 Kinase

TC21(R-Ras2), a Ras-related GTPase with transforming potential similar to H-, K- and N-Ras, is implicated in the pathogenesis of human cancers. Transforming growth factor β (TGF-β), a cytokine that plays a significant role in modulating tumorigenesis, normally prevents uncontrolled cell proliferation but paradoxically induces proliferation in H-Ras-transformed cancer cells. Although TC21 activates some pathways that mediate cellular transformation by the classical Ras proteins, the mechanisms through which TC21 induces tumor formation and how TGF-β regulates TC21 transformed cells is not known. To better understand the role of TC21 in cancer progression, we overexpressed an activated G23V mutant of TC21 in a nontumorigenic murine mammary epithelial (EpH4) cell line. Mutant TC21-expressing cells were significantly more oncogenic than cells expressing activated G12V H-Ras both in vivo and in vitro. TC21-induced transformation and proliferation required activation of p38 MAPK, mTOR (the mammalian target of rapamycin), and phosphoinositide 3-kinase but not Akt/PKB. Transformation by TC21 rendered EpH4 cells insensitive to the growth inhibitory effects of TGF-β, and the soft agar growth of these cells was increased upon TGF-β stimulation. Despite losing responsiveness to TGF-β-mediated growth inhibition, both Smad-dependent and independent pathways remained intact in TC21-transformed cells. Thus, overexpression of active TC21 in EpH4 cells induces tumorigenicity through the phosphoinositide 3-kinase, p38 MAPK, and mTOR pathways, and these cells lose their sensitivity to the normal growth inhibitory role of TGF-β.

scholarly journals ICSBP-mediated immune protection against BCR-ABL–induced leukemia requires the CCL6 and CCL9 chemokines

Blood ◽  
2009 ◽  
Vol 113 (16) ◽  
pp. 3813-3820 ◽  
Author(s):  
Valentina Nardi ◽  
Olaia Naveiras ◽  
Mohammad Azam ◽  
George Q. Daley
Keyword(s):  
Murine Model ◽  
Consensus Sequence ◽  
Myelogenous Leukemia ◽  
Transformed Cells ◽  
Type I ◽  
Immune Protection ◽  
Immune Mechanism ◽  
Type I Ifns ◽  
New Strategies

Abstract Interferon (IFN) is effective at inducing complete remissions in patients with chronic myelogenous leukemia (CML), and evidence supports an immune mechanism. Here we show that the type I IFNs (alpha and beta) regulate expression of the IFN consensus sequence-binding protein (ICSBP) in BCR-ABL–transformed cells and as shown previously for ICSBP, induce a vaccine-like immunoprotective effect in a murine model of BCR-ABL–induced leukemia. We identify the chemokines CCL6 and CCL9 as genes prominently induced by the type I IFNs and ICSBP, and demonstrate that these immunomodulators are required for the immunoprotective effect of ICSBP expression. Insights into the role of these chemokines in the antileukemic response of IFNs suggest new strategies for immunotherapy of CML.

scholarly journals A Critical Role of Glutamine and Asparagine γ-Nitrogen in Nucleotide Biosynthesis in Cancer Cells Hijacked by an Oncogenic Virus

mBio ◽  
2017 ◽  
Vol 8 (4) ◽  
Author(s):  
Ying Zhu ◽  
Tingting Li ◽  
Suzane Ramos da Silva ◽  
Jae-Jin Lee ◽  
Chun Lu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cancer Cells ◽  
Metabolic Pathway ◽  
Tca Cycle ◽  
Glutamine Metabolism ◽  
Transformed Cells ◽  
Oncogenic Virus ◽  
Phosphoribosyl Pyrophosphate ◽  
Rate Limiting

ABSTRACT While glutamine is a nonessential amino acid that can be synthesized from glucose, some cancer cells primarily depend on glutamine for their growth, proliferation, and survival. Numerous types of cancer also depend on asparagine for cell proliferation. The underlying mechanisms of the glutamine and asparagine requirement in cancer cells in different contexts remain unclear. In this study, we show that the oncogenic virus Kaposi’s sarcoma-associated herpesvirus (KSHV) accelerates the glutamine metabolism of glucose-independent proliferation of cancer cells by upregulating the expression of numerous critical enzymes, including glutaminase 2 (GLS2), glutamate dehydrogenase 1 (GLUD1), and glutamic-oxaloacetic transaminase 2 (GOT2), to support cell proliferation. Surprisingly, cell crisis is rescued only completely by supplementation with asparagine but minimally by supplementation with α-ketoglutarate, aspartate, or glutamate upon glutamine deprivation, implying an essential role of γ-nitrogen in glutamine and asparagine for cell proliferation. Specifically, glutamine and asparagine provide the critical γ-nitrogen for purine and pyrimidine biosynthesis, as knockdown of four rate-limiting enzymes in the pathways, including carbamoylphosphate synthetase 2 (CAD), phosphoribosyl pyrophosphate amidotransferase (PPAT), and phosphoribosyl pyrophosphate synthetases 1 and 2 (PRPS1 and PRPS2, respectively), suppresses cell proliferation. These findings indicate that glutamine and asparagine are shunted to the biosynthesis of nucleotides and nonessential amino acids from the tricarboxylic acid (TCA) cycle to support the anabolic proliferation of KSHV-transformed cells. Our results illustrate a novel mechanism by which an oncogenic virus hijacks a metabolic pathway for cell proliferation and imply potential therapeutic applications in specific types of cancer that depend on this pathway. IMPORTANCE We have previously found that Kaposi’s sarcoma-associated herpesvirus (KSHV) can efficiently infect and transform primary mesenchymal stem cells; however, the metabolic pathways supporting the anabolic proliferation of KSHV-transformed cells remain unknown. Glutamine and asparagine are essential for supporting the growth, proliferation, and survival of some cancer cells. In this study, we have found that KSHV accelerates glutamine metabolism by upregulating numerous critical metabolic enzymes. Unlike most cancer cells that primarily utilize glutamine and asparagine to replenish the TCA cycle, KSHV-transformed cells depend on glutamine and asparagine for providing γ-nitrogen for purine and pyrimidine biosynthesis. We identified four rate-limiting enzymes in this pathway that are essential for the proliferation of KSHV-transformed cells. Our results demonstrate a novel mechanism by which an oncogenic virus hijacks a metabolic pathway for cell proliferation and imply potential therapeutic applications in specific types of cancer that depend on this pathway.

scholarly journals SKIP Downregulation Increases TGF-β1-Induced Matrix Metalloproteinase-9 Production in Transformed Keratinocytes

Scientifica ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jelena Kocić ◽  
Victor Villar ◽  
Aleksandra Krstić ◽  
Juan F. Santibanez
Keyword(s):  
Matrix Metalloproteinase ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Regulatory Protein ◽  
Mek Inhibitor ◽  
Matrix Metalloproteinase 9 ◽  
Transformed Cells ◽  
Interacting Protein ◽  
Metalloproteinase 9

Transforming growth factor-beta (TGF-β1) is a potent inductor of matrix metalloproteinase-9 (MMP-9) in transformed cells. Recently, Ski-interacting protein (SKIP) has been described as a regulator of TGF-β1 signal transduction, but its role in the induction of cell malignance by TGF-β1 has not been fully elucidated so far. In the present study, we analyzed the role of SKIP on TGF-β1-induced MMP-9 production. Mouse transformed keratinocytes (PDV) were stably transfected with SKIP antisense construct. We observed that SKIP depletion provoked an enhancement in the expression of MMP-9 in response to TGF-β1 treatment. The downregulation of SKIP produced an enhancement in TGF-β1-activated ERK1,2 MAP kinase as well as increased transactivation of downstream Elk1 transcription factor. The increased MMP-9 production in response to TGF-β1 was dependent of MAPK activation as PD98059, an MEK inhibitor, reduced MMP-9 expression in SKIP antisense transfected cells. Thus, we propose SKIP as a regulatory protein in TGF-β1-induced MMP-9 expression acting by controlling ERK1,2 signaling in transformed cells.

scholarly journals The roles of distinct Ca2+ signaling mediated by Piezo and inositol triphosphate receptor (IP3R) in the remodeling of E-cadherin during cell dissemination

2021 ◽  
Author(s):  
Alejandra J.H. Cabrera ◽  
Barry M Gumbiner ◽  
Young V Kwon
Keyword(s):  
Calcium Signaling ◽  
Intracellular Calcium ◽  
Cell Invasion ◽  
Adherens Junctions ◽  
Transformed Cells ◽  
Inositol Triphosphate ◽  
Intracellular Calcium Signaling ◽  
Cell Dissemination

Given the role of E-cadherin (E-cad) in holding epithelial cells together, the inverse relationship between E-cad levels and cell invasion has been perceived as a principle underlying the invasiveness of tumor cells. In contrast, our study employing the Drosophila model of cell dissemination demonstrates that E-cad is necessary for the invasiveness of RasV12-transformed cells in vivo. Drosophila E-cad/β-catenin disassembles at adherens junctions and assembles at invasive protrusions—the actin- and cortactin-rich invadopodia-like protrusions associated with breach of the extracellular matrix (ECM)—during cell dissemination. Loss of E-cad attenuates dissemination of RasV12-transformed cells by impairing their ability to compromise the ECM. Strikingly, the remodeling of E-cad/β-catenin subcellular distribution is controlled by two discrete intracellular calcium signaling pathways: Ca2+ release from endoplasmic reticulum via the inositol triphosphate receptor (IP3R) disassembles E-cad at adherens junctions while Ca2+ entry via the mechanosensitive channel Piezo assembles E-cad at invasive protrusions. Thus, our study provides molecular insights into the unconventional role of E-cad in cell invasion during cell dissemination in vivo and describes the discrete roles of intracellular calcium signaling in the remodeling of E-cad/β-catenin subcellular localization.

scholarly journals The Role of E4BP4 in Apoptosis of Human Leukemia Cells in Culture

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Erick Lenin Mitchell‐Velasquez ◽  
Danny Gomez ◽  
Rheem D Medh
Keyword(s):  
Leukemia Cells ◽  
Human Leukemia ◽  
Cells In Culture ◽  
Human Leukemia Cells
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