Microreviews

Coping with the calcium overload caused by cell injury: ER to the rescue

Goutam Chandra1,2, Davi A. G. Mázala1,3 and Jyoti K. Jaiswal1,4

It was nearly a century ago that Lewis Victor Heilbrunn identified the requirement of extracellular Ca2+ for what he termed as ‘surface precipitation reaction‘, a process that allows the cytoplasm

Inhibitory DAMPs in immunogenic cell death and its clinical implications

Kazukuni Hayashi1,2, Fotis Nikolos3 and Keith S. Chan1,3

– [table id=388/] INHIBITORY DAMP OR INHIBITORY DAMPS? How are immunostimulatory DAMPs shut off? Under normal physiological conditions, the co-stimulatory molecules, CD80/86, on antigen presenting cells bind to the co-activating

Targeting FBXO44/SUV39H1 elicits tumor cell-specific DNA replication stress and viral mimicry

Jia Z. Shen1 and Charles Spruck1

Repetitive elements (REs) are normally transcriptionally silenced in somatic cells by repressive epigenetic modifications, which are thought to include DNA methylation and histone modifications such as deacetylation, H3K9me3, and H4K20me3. Although, it is unclear how RE silencing is maintained through DNA replication cycles in rapidly growing cancer cells. On the other hand, the reactivation of endogenous retroelements beyond a threshold level of tolerance in cancer cells, such as by treatment with DNA demethylating agents or HDAC or LSD1 inhibitors, can induce viral mimicry responses that augment certain cancer therapies, including immunotherapy. However, these agents can also affect normal cells presenting obvious side effects. Therefore, uncovering cancer cell-specific RE silencing mechanisms could provide a basis for the development of a new generation of cancer (...)

The OFD1 protein is a novel player in selective autophagy: another tile to the cilia/autophagy puzzle

Manuela Morleo1 and Brunella Franco1,2

Autophagy is an evolutionary conserved and highly regulated cellular degradation pathway which entails the engulfment of cellular components into double-membrane vesicles, called autophagosomes, which then fuse with lysosomes to degrade

Innate RIG-I signaling restores antigen presentation in tumors and overcomes T cell resistance

Beatrice Thier1,2 and Annette Paschen1,2

In recent years, therapy with immune modulating antibodies, termed immune checkpoint blockade (ICB), has revolutionized the treatment of advanced metastatic melanoma, yielding long-lasting clinical responses in a subgroup of patients. But despite this remarkable progress, resistance to therapy represents a major clinical challenge. ICB efficacy is critically dependent on cytotoxic CD8+ T cells targeting tumor cells in an HLA class I (HLA-I) antigen-dependent manner. Transcriptional suppression of the HLA-I antigen processing and presentation machinery (HLA-I APM) in melanoma cells leads to HLA-I-low/-negative tumor cell phenotypes escaping CD8+ T cell recognition and contributing to ICB resistance. In general, HLA-I-low/-negative tumor cells can be re-sensitized to T cells by interferons (IFN), augmenting HLA-I APM expression. However, this mechanism fails when melanoma cells acquire resistance to IFN, which recently turned out as a key resistance mechanism in (...)

Mitochondrial dynamics links PINCH-1 signaling to proline metabolic reprogramming and tumor growth

Ling Guo1 and Chuanyue Wu2

How does PINCH-1 regulate proline synthesis? Proline is synthesized in cells through reduction of Δ1-pyrroline-5-carboxylate (P5C) with NAD(P)H as an electron donor, a reaction catalyzed by pyrroline-5-carboxylate reductase (PYCR). Three

To promote or inhibit glioma progression, that is the question for IL-33

Stephen M. Robbins1 and Donna L. Senger1

Glioblastoma represents one of the most fatal of human cancers. Although there has been progress in the treatment of glioblastoma as a result of a treatment regimen that combines maximal

AMPK maintains TCA cycle through sequential phosphorylation of PDHA to promote tumor metastasis

Zhen Cai1,#, Danni Peng1,# and Hui-Kuan Lin1

Although cancer metastasis represents the main cause for cancer-related death, the underlying mechanism involved in cancer metastasis remains largely unknown. The lack of the clear understanding of cancer metastasis has

TLR4: the fall guy in sepsis?

Joseph Menassa1, Christina Nedeva1, Corey Pollock1 and Hamsa Puthalakath1

WHOLE GENOME CRISPR SCREEN AND THE IDENTIFICATION OF Treml4 We reasoned that if immune cells undergo apoptosis during sepsis, ablation of the gene responsible for this in a sub-population should

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