scholarly journals Integrin Signaling in Cancer Cell Survival and Chemoresistance

2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Fawzi Aoudjit ◽  
Kristiina Vuori
Keyword(s):  
Cell Survival ◽  
Cancer Cell ◽  
Antibody Therapy ◽  
Cancer Recurrence ◽  
Critical Factor ◽  
Cell Types ◽  
Integrin Signaling ◽  
Drug Induced ◽  
Major Pathway ◽  
Cancer Cell Survival

Resistance to apoptosis and chemotherapy is a hallmark of cancer cells, and it is a critical factor in cancer recurrence and patient relapse. Extracellular matrix (ECM) via its receptors, the integrins, has emerged as a major pathway contributing to cancer cell survival and resistance to chemotherapy. Several studies over the last decade have demonstrated that ECM/integrin signaling provides a survival advantage to various cancer cell types against numerous chemotherapeutic drugs and against antibody therapy. In this paper, we will discuss the major findings on how ECM/integrin signaling protects tumor cells from drug-induced apoptosis. We will also discuss the potential role of ECM in malignant T-cell survival and in cancer stem cell resistance. Understanding how integrins and their signaling partners promote tumor cell survival and chemoresistance will likely lead to the development of new therapeutic strategies and agents for cancer treatment.

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 γ-Synuclein Promotes Cancer Cell Survival and Inhibits Stress- and Chemotherapy Drug-induced Apoptosis by Modulating MAPK Pathways

2002 ◽  
Vol 277 (38) ◽  
pp. 35050-35060 ◽  
Author(s):  
Zhong-Zong Pan ◽  
Wendy Bruening ◽  
Benoit I. Giasson ◽  
Virginia M.-Y. Lee ◽  
Andrew K. Godwin
Keyword(s):  
Cell Survival ◽  
Cancer Cell ◽  
Drug Induced ◽  
Chemotherapy Drug ◽  
Mapk Pathways ◽  
Cancer Cell Survival ◽  
Induced Apoptosis

scholarly journals 14-3-3ζ Overexpression Defines High Risk for Breast Cancer Recurrence and Promotes Cancer Cell Survival

2009 ◽  
Vol 69 (8) ◽  
pp. 3425-3432 ◽  
Author(s):  
Christopher L. Neal ◽  
Jun Yao ◽  
Wentao Yang ◽  
Xiaoyan Zhou ◽  
Nina T. Nguyen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cell Survival ◽  
Cancer Cell ◽  
Cancer Recurrence ◽  
Breast Cancer Recurrence ◽  
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

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.

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