scholarly journals Lipid raft involvement in signal transduction in cancer cell survival, cell death and metastasis

2021 ◽  
Author(s):  
Borui Li ◽  
Yi Qin ◽  
Xianjun Yu ◽  
Xiaowu Xu ◽  
Wenyan Yu
Keyword(s):  
Signal Transduction ◽  
Cell Death ◽  
Cell Survival ◽  
Cancer Cell ◽  
Lipid Raft ◽  
Cancer Cell Survival

scholarly journals LONP1 and ClpP cooperatively regulate mitochondrial proteostasis for cancer cell survival

Oncogenesis ◽  
2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Yu Geon Lee ◽  
Hui Won Kim ◽  
Yeji Nam ◽  
Kyeong Jin Shin ◽  
Yu Jin Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Growth ◽  
Cell Survival ◽  
Cancer Cell ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Tca Cycle ◽  
Mitochondrial Matrix ◽  
Mitochondrial Functions ◽  
Cancer Cell Survival

AbstractMitochondrial proteases are key components in mitochondrial stress responses that maintain proteostasis and mitochondrial integrity in harsh environmental conditions, which leads to the acquisition of aggressive phenotypes, including chemoresistance and metastasis. However, the molecular mechanisms and exact role of mitochondrial proteases in cancer remain largely unexplored. Here, we identified functional crosstalk between LONP1 and ClpP, which are two mitochondrial matrix proteases that cooperate to attenuate proteotoxic stress and protect mitochondrial functions for cancer cell survival. LONP1 and ClpP genes closely localized on chromosome 19 and were co-expressed at high levels in most human cancers. Depletion of both genes synergistically attenuated cancer cell growth and induced cell death due to impaired mitochondrial functions and increased oxidative stress. Using mitochondrial matrix proteomic analysis with an engineered peroxidase (APEX)-mediated proximity biotinylation method, we identified the specific target substrates of these proteases, which were crucial components of mitochondrial functions, including oxidative phosphorylation, the TCA cycle, and amino acid and lipid metabolism. Furthermore, we found that LONP1 and ClpP shared many substrates, including serine hydroxymethyltransferase 2 (SHMT2). Inhibition of both LONP1 and ClpP additively increased the amount of unfolded SHMT2 protein and enhanced sensitivity to SHMT2 inhibitor, resulting in significantly reduced cell growth and increased cell death under metabolic stress. Additionally, prostate cancer patients with higher LONP1 and ClpP expression exhibited poorer survival. These results suggest that interventions targeting the mitochondrial proteostasis network via LONP1 and ClpP could be potential therapeutic strategies for cancer.

Targeting autophagy for the treatment of cancer

2018 ◽  
Vol 399 (7) ◽  
pp. 673-677 ◽  
Author(s):  
Simone Fulda
Keyword(s):  
Cell Death ◽  
Drug Treatment ◽  
Cell Survival ◽  
Cancer Cell ◽  
Anticancer Drug ◽  
Autophagic Cell Death ◽  
Eukaryotic Cells ◽  
Drug Induced ◽  
Cancer Cell Survival ◽  
Catabolic Process

Abstract Macroautophagy (herein termed autophagy) is evolutionarily highly conserved across eukaryotic cells and represents an intracellular catabolic process that targets damaged macromolecules and organelles for degradation. Autophagy is dysregulated in various human diseases including cancer. In addition, many drugs currently used for the treatment of cancer can engage autophagy, which typically promotes cancer cell survival by mitigating cellular stress. However, under certain circumstances activation of autophagy upon anticancer drug treatment can also trigger a lethal type of autophagy termed autophagic cell death (ACD). This may pave new avenues for exploiting the autophagic circuitry in oncology. This review presents the concept and some examples of anticancer drug-induced ACD.

scholarly journals ATM inhibition drives metabolic adaptation via induction of macropinocytosis

2020 ◽  
Author(s):  
Chi-Wei Chen ◽  
Raquel Buj ◽  
Erika S. Dahl ◽  
Kelly E. Leon ◽  
Erika L. Varner ◽  
...  
Keyword(s):  
Cell Death ◽  
Cell Survival ◽  
Cancer Cell ◽  
Metabolic Reprogramming ◽  
Metabolic Adaptation ◽  
Dependent Manner ◽  
Cancer Cell Survival ◽  
Branched Chain

SummaryMacropinocytosis is a nonspecific endocytic process that enhances cancer cell survival under nutrient-poor conditions. Ataxia-Telangiectasia mutated (ATM) is a tumor suppressor that plays a role in cellular metabolic reprogramming. We report that suppression of ATM increases macropinocytosis in an AMPK-dependent manner to promote cancer cell survival in nutrient-poor conditions. Combined inhibition of ATM and macropinocytosis suppressed proliferation and induced cell death both in vitro and in vivo. Metabolite analysis of the ascites and interstitial fluid from tumors indicated decreased branched chain amino acids (BCAAs) in the microenvironment of ATM-inhibited tumors. Supplementation of ATM inhibitor-treated cells with BCAAs abrogated AMPK phosphorylation and macropinocytosis and rescued the cell death that occurs due to combined inhibition of ATM and macropinocytosis. These data reveal a novel molecular basis of ATM-mediated tumor suppression whereby loss of ATM promotes pro-tumorigenic uptake of nutrients to promote cancer cell survival and reveal a metabolic vulnerability of ATM-inhibited cells.

Malaria drug halts cancer cell survival

2018 ◽  
Author(s):  
Sarah Elmeshad
Keyword(s):  
Cell Survival ◽  
Cancer Cell ◽  
Cancer Cell Survival

Polyphosphate Affects Breast Cancer Cell Survival

2006 ◽  
Author(s):  
Christine Haakenson
Keyword(s):  
Breast Cancer ◽  
Cell Survival ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Survival

Co-targeting EGFR and Autophagy Impairs Ovarian Cancer Cell Survival during Detachment from the ECM

2015 ◽  
Vol 15 (3) ◽  
pp. 215-226 ◽  
Author(s):  
Zongyuan Yang ◽  
Yi Liu ◽  
Xiao Wei ◽  
Xiaoshui Zhou ◽  
Cheng Gong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Survival ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Cancer Cell Survival

AMPA Receptor Antagonist CFM-2 Decreases Survivin Expression in Cancer Cells

2018 ◽  
Vol 18 (4) ◽  
pp. 591-596 ◽  
Author(s):  
Domingo Sanchez Ruiz ◽  
Hella Luksch ◽  
Marco Sifringer ◽  
Achim Temme ◽  
Christian Staufner ◽  
...  
Keyword(s):  
Cell Survival ◽  
Receptor Antagonist ◽  
Cancer Cells ◽  
Glutamate Receptors ◽  
Cancer Cell ◽  
Ampa Receptor ◽  
Ampa Receptors ◽  
Survivin Expression ◽  
Ampa Receptor Antagonist ◽  
Cancer Cell Survival

Background: Glutamate receptors are widely expressed in different types of cancer cells. α-Amino-3- hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors are ionotropic glutamate receptors which are coupled to intracellular signaling pathways that influence cancer cell survival, proliferation, and migration. Blockade of AMPA receptors by pharmacologic compounds may potentially constitute an effective tool in anticancer treatment strategies. Method: Here we investigated the impact of the AMPA receptor antagonist CFM-2 on the expression of the protein survivin, which is known to promote cancer cell survival and proliferation. We show that CFM-2 inhibits survivin expression at mRNA and protein levels and decreases the viability of cancer cells. Using a stably transfected cell line which overexpresses survivin, we demonstrate that over-expression of survivin enhances cancer cell viability and attenuates CFM-2–mediated inhibition of cancer cell growth. Result: These findings point towards suppression of survivin expression as a new mechanism contributing to anticancer effects of AMPA antagonists.

scholarly journals The ERG-Regulated LINC00920 Promotes Prostate Cancer Cell Survival via the 14-3-3ε–FOXO Pathway

2020 ◽  
Vol 18 (10) ◽  
pp. 1545-1559
Author(s):  
Arlou Kristina Angeles ◽  
Doreen Heckmann ◽  
Niclas Flosdorf ◽  
Stefan Duensing ◽  
Holger Sültmann
Keyword(s):  
Prostate Cancer ◽  
Cell Survival ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Cancer Cell Survival

Fr154 SMOKING INDUCES WEE1 EXPRESSION PROMOTING CANCER CELL SURVIVAL IN ESOPHAGEAL ADENOCARCINOMA

2021 ◽  
Vol 160 (6) ◽  
pp. S-240
Author(s):  
Zheng Chen ◽  
Heng Lu ◽  
Dunfa Peng ◽  
Wael El-Rifai
Keyword(s):  
Cell Survival ◽  
Esophageal Adenocarcinoma ◽  
Cancer Cell ◽  
Cancer Cell Survival
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