BAP1 links metabolic regulation of ferroptosis to tumour suppression

Nature Cell Biology, Год журнала: 2018, Номер 20(10), С. 1181 - 1192

Опубликована: Сен. 3, 2018

Язык: Английский

---

Autophagy-Independent Functions of the Autophagy Machinery

Cell, Год журнала: 2019, Номер 177(7), С. 1682 - 1699

Опубликована: Июнь 1, 2019

Язык: Английский

---

Necroptosis: Mechanisms and Relevance to Disease

Annual Review of Pathology Mechanisms of Disease, Год журнала: 2016, Номер 12(1), С. 103 - 130

Опубликована: Дек. 13, 2016

Necroptosis is a form of regulated cell death that critically depends on receptor-interacting serine-threonine kinase 3 (RIPK3) and mixed lineage domain-like (MLKL) generally manifests with morphological features necrosis. The molecular mechanisms underlie distinct instances necroptosis have just begun to emerge. Nonetheless, it has already been shown contributes cellular demise in various pathophysiological conditions, including viral infection, acute kidney injury, cardiac ischemia/reperfusion. Moreover, human tumors appear obtain an advantage from the downregulation key components machinery for necroptosis. Although such may stem increased resistance adverse microenvironmental accumulating evidence indicates necroptosis-deficient cancer cells are poorly immunogenic hence escape natural therapy-elicited immunosurveillance. Here, we discuss relevance disease

Язык: Английский

---

Regulated necrosis: disease relevance and therapeutic opportunities

Nature Reviews Drug Discovery, Год журнала: 2016, Номер 15(5), С. 348 - 366

Опубликована: Янв. 18, 2016

Язык: Английский

---

The role of ubiquitination in tumorigenesis and targeted drug discovery

Signal Transduction and Targeted Therapy, Год журнала: 2020, Номер 5(1)

Опубликована: Фев. 29, 2020

Ubiquitination, an important type of protein posttranslational modification (PTM), plays a crucial role in controlling substrate degradation and subsequently mediates the "quantity" "quality" various proteins, serving to ensure cell homeostasis guarantee life activities. The regulation ubiquitination is multifaceted works not only at transcriptional levels (phosphorylation, acetylation, methylation, etc.) but also level (activators or repressors). When regulatory mechanisms are aberrant, altered biological processes may induce serious human diseases, especially types cancer. In tumorigenesis, involve tumor metabolism, immunological microenvironment (TME), cancer stem (CSC) stemness so on. With regard some key proteins such as RagA, mTOR, PTEN, AKT, c-Myc P53 significantly regulates activity mTORC1, AMPK PTEN-AKT signaling pathways. addition, TLR, RLR STING-dependent pathways modulates TME. Moreover, core regulator triplets (Nanog, Oct4 Sox2) members Wnt Hippo-YAP participates maintenance CSC stemness. Based on components, including proteasome, E3 ligases, E1, E2 deubiquitinases (DUBs), many molecular targeted drugs have been developed combat Among them, small molecule inhibitors targeting bortezomib, carfilzomib, oprozomib ixazomib, achieved tangible success. MLN7243 MLN4924 (targeting E1 enzyme), Leucettamol A CC0651 nutlin MI-219 compounds G5 F6 DUB activity) shown potential preclinical treatment. this review, we summarize latest progress understanding substrates for their special functions metabolism regulation, TME modulation maintenance. therapeutic targets reviewed, effects drugs.

Язык: Английский

---

The interaction between ferroptosis and lipid metabolism in cancer

Signal Transduction and Targeted Therapy, Год журнала: 2020, Номер 5(1)

Опубликована: Июнь 30, 2020

Abstract Ferroptosis is a new form of programmed cell death characterized by the accumulation iron-dependent lethal lipid peroxides. Recent discoveries have focused on alterations that occur in metabolism during ferroptosis and provided intriguing insights into interplay between cancer. Their interaction regulates initiation, development, metastasis, therapy resistance cancer, as well tumor immunity, which offers several potential strategies for cancer treatment. This review brief overview features characterizing metabolism, highlights significance this

Язык: Английский

---

The Mitochondrial Permeability Transition Pore: Channel Formation by F-ATP Synthase, Integration in Signal Transduction, and Role in Pathophysiology

Physiological Reviews, Год журнала: 2015, Номер 95(4), С. 1111 - 1155

Опубликована: Авг. 13, 2015

The mitochondrial permeability transition (PT) is a increase of the inner membrane mediated by channel, pore (PTP). After brief historical introduction, we cover key regulatory features PTP and provide critical assessment putative protein components that have been tested genetic analysis. discovery under conditions oxidative stress F-ATP synthases mammals, yeast, Drosophila can be turned into Ca(2+)-dependent channels, whose electrophysiological properties match those corresponding PTPs, opens new perspectives to field. We discuss structural functional may clues its from an energy-conserving energy-dissipating device as well recent advances on signal transduction role in cellular pathophysiology.

Язык: Английский

---

ASCT2/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer

Oncogene, Год журнала: 2015, Номер 35(24), С. 3201 - 3208

Опубликована: Окт. 12, 2015

Alanine, serine, cysteine-preferring transporter 2 (ASCT2; SLC1A5) mediates uptake of glutamine, a conditionally essential amino acid in rapidly proliferating tumour cells. Uptake glutamine and subsequent glutaminolysis is critical for activation the mTORC1 nutrient-sensing pathway, which regulates cell growth protein translation cancer This particular interest breast cancer, as dependence increased high-risk subtypes. Pharmacological inhibitors ASCT2-mediated transport significantly reduced human lines, leading to suppression signalling, cycle progression. Notably, these effects were subtype-dependent, with ASCT2 only triple-negative (TN) basal-like compared minimal luminal Both stable inducible shRNA-mediated knockdown confirmed that inhibiting function was sufficient prevent cellular proliferation induce rapid death TN cells, but not Using bioluminescent orthotopic xenograft mouse model, expression then shown be necessary both successful engraftment HCC1806 cells vivo. Lower tumoral conferred significant survival advantage xenografted mice. These responses remained intact primary cancers, where gene analysis showed high metabolism-related genes, including GLUL GLS, cohort 90 patients, well correlations transcriptional regulators, MYC ATF4. study provides preclinical evidence feasibility novel therapies exploiting activity particularly subgroup there ASCT2, also marked reliance on its sustained proliferation.

Язык: Английский

---

Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA

Cell Death and Differentiation, Год журнала: 2019, Номер 26(11), С. 2329 - 2343

Опубликована: Фев. 20, 2019

The regulatory loop between long noncoding RNAs (lncRNAs) and microRNAs has a dynamic role in transcriptional translational regulation, is involved cancer. However, the circuitry lncRNAs tumorigenesis remains elusive. Here we demonstrate that nuclear lncRNA LINC00336 upregulated lung cancer functions as an oncogene by acting competing endogenous RNA (ceRNAs). bound RNA-binding protein ELAVL1 (ELAV-like 1) using nucleotides 1901–2107 of RRM interaction domain key amino acids (aa) (aa 101–213), inhibiting ferroptosis. Moreover, increased expression stabilizing its posttranscriptional level, whereas LSH (lymphoid-specific helicase) through p53 signaling pathway, further supporting hypothesis promotes expression. Interestingly, served sponge microRNA 6852 (MIR6852) to regulate cystathionine-β-synthase (CBS), surrogate marker Finally, found MIR6852 inhibited cell growth promoting These data show network ceRNA important

Язык: Английский

---

Classification of current anticancer immunotherapies

Oncotarget, Год журнала: 2014, Номер 5(24), С. 12472 - 12508

Опубликована: Дек. 18, 2014

During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to robust clinical reality. Many immunotherapeutic regimens are now approved by US Food and Drug Administration European Medicines Agency for use in cancer patients, many others being investigated as standalone interventions or combined with conventional treatments studies. Immunotherapies may be subdivided into "passive" "active" based on their ability engage host immune system against cancer. Since activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies system, this classification does not properly reflect complexity drug-host-tumor interaction. Alternatively, can classified according antigen specificity. While some immunotherapies specifically target one (or few) defined tumor-associated antigen(s), operate relatively non-specific manner boost natural therapy-elicited responses unknown often broad Here, we propose critical, integrated discuss relevance these approaches.

Язык: Английский

---