Nucleus-translocated glucokinase functions as a protein kinase to phosphorylate TAZ and promote tumour growth.

Hypoxia frequently occurs during rapid tumour growth. However, how tumour cells adapt to hypoxic stress by remodeling central cellular pathways remains largely unclear. Here, we show that hypoxia induces casein kinase 2 (CK2)-mediated glucokinase (GCK) S398 phosphorylation, which exposes its nuclear localization signal (NLS) for importin α1 binding and nuclear translocation.

CLOCK promotes proliferation of glioblastoma cells through acetylating PRPS1/2.

Purpose: The oncogenic impairment of the circadian clock plays an important role in tumorigenesis. However, it remains unclear whether the activation of epidermal growth factor (EGF) receptor (EGFR), which plays a critical role in glioblastoma (GBM) development, regulates the circadian clock and thereby tumorigenesis.

Methods: This study employed molecular techniques including DNA mutagenesis, qPCR, immunoprecipitation, immunofluorescence, and functional assays.

A Mallows-like criterion for anomaly detection with random forest implementation.

Anomaly detection plays a crucial role in fields such as information security and industrial production. It relies on the identification of rare instances that deviate significantly from expected patterns. Reliance on a single model can introduce uncertainty, as it may not adequately capture the complexity and variability inherent in real-world datasets.

Moonlighting functions of glucose metabolic enzymes and metabolites in cancer.

Glucose metabolic enzymes and their metabolites not only provide energy and building blocks for synthesizing macromolecules but also possess non-canonical or moonlighting functions in response to extracellular and intracellular signalling. These moonlighting functions modulate various cellular activities, including gene expression, cell cycle progression, DNA repair, autophagy, senescence and apoptosis, cell proliferation, remodelling of the tumour microenvironment and immune responses. These functions integrate glucose metabolism with other essential cellular activities, driving cancer progression.

Targeting Trop2 in solid tumors: a look into structures and novel epitopes.

Trophoblast cell surface antigen 2 (Trop2) exhibits limited expression in normal tissues but is over-expressed across various solid tumors. The effectiveness of anti-Trop2 antibody-drug conjugate (ADC) in managing breast cancer validates Trop2 as a promising therapeutic target for cancer treatment. However, excessive toxicity and a low response rate of ADCs pose ongoing challenges.

The moonlighting function of glycolytic enzyme enolase-1 promotes choline phospholipid metabolism and tumor cell proliferation.

Aberrantly upregulated choline phospholipid metabolism is a novel emerging hallmark of cancer, and choline kinase α (CHKα), a key enzyme for phosphatidylcholine production, is overexpressed in many types of human cancer through undefined mechanisms. Here, we demonstrate that the expression levels of the glycolytic enzyme enolase-1 (ENO1) are positively correlated with CHKα expression levels in human glioblastoma specimens and that ENO1 tightly governs CHKα expression via posttranslational regulation. Mechanistically, we reveal that both ENO1 and the ubiquitin E3 ligase TRIM25 are associated with CHKα.

Tetrazine bioorthogonal chemistry makes nanotechnology a powerful toolbox for biological applications.

Bioorthogonal chemistry enables researchers to manipulate bioactive molecules in living systems. These highly selective and biocompatible reactions can be carried out in various complex environments. Over the past two decades, a considerable number of strides have been made to expand the capacities of bioorthogonal chemistry coupled with the aim to fine-tune present reactions for specific applications.

Tetrazine bioorthogonal chemistry derived imaging.

Bioorthogonal chemistry represents plenty of highly efficient and biocompatible reactions that proceed selectively and rapidly in biological situations without unexpected side reactions towards miscellaneous endogenous functional groups. Arise from the strict demands of physiological reactions, bioorthogonal chemical reactions are natively selective transformations that are rarely found in biological environments. Bioorthogonal chemistry has long been applied to tracking and real-time imaging of biomolecules in their physiological environments.

METTL3 promotes tumour development by decreasing APC expression mediated by APC mRNA N-methyladenosine-dependent YTHDF binding.

The adenomatous polyposis coli (APC) is a frequently mutated tumour suppressor gene in cancers. However, whether APC is regulated at the epitranscriptomic level remains elusive. In this study, we analysed TCGA data and separated 200 paired oesophageal squamous cell carcinoma (ESCC) specimens and their adjacent normal tissues and demonstrated that methyltransferase-like 3 (METTL3) is highly expressed in tumour tissues.

Prognostic Impact of PCK1 Protein Kinase Activity-Dependent Nuclear SREBP1 Activation in Non-Small-Cell Lung Carcinoma.

Metabolic enzymes can perform non-metabolic functions and play critical roles in the regulation of a variety of important cellular activities. Phosphoenolpyruvate carboxykinase 1 (PCK1), a gluconeogenesis enzyme, was recently identified as an AKT-regulated protein kinase that phosphorylates INSIG1/2 to promote nuclear SREBP1-dependent lipogenesis. However, the relationship of this regulation with the progression of non-small-cell lung carcinoma (NSCLC) is unclear.

Association of phosphoenolpyruvate carboxykinase 1 protein kinase activity-dependent sterol regulatory element-binding protein 1 activation with prognosis of oesophageal carcinoma.

Background: Metabolic enzymes have non-canonical functions and play vital roles in the regulation of various cellular activities. Phosphoenolpyruvate carboxykinase 1 (PCK1), a gluconeogenic enzyme, was recently identified as an AKT-dependent protein kinase and promoted sterol regulatory element-binding protein 1 (SREBP1)-dependent lipogenesis. However, association of this protein kinase activity of PCK1 with progression of oesophageal squamous cell carcinoma (ESCC) is unclear.

Keratin 14-high subpopulation mediates lung cancer metastasis potentially through Gkn1 upregulation.

Metastasis is the leading cause of lung cancer-related death. Elucidating the metastasis process can provide new avenues to inhibit this malignant behavior of cancer cells. Here we found that human lung cancers with high Keratin 14 (K14) expression were associated with nodal metastasis and poor survival.

Cullin5 deficiency promotes small-cell lung cancer metastasis by stabilizing integrin β1.

Metastasis is the dominant cause of patient death in small-cell lung cancer (SCLC), and a better understanding of the molecular mechanisms underlying SCLC metastasis may potentially improve clinical treatment. Through genome-scale screening for key regulators of mouse Rb1-/- Trp53-/- SCLC metastasis using the pooled CRISPR/Cas9 library, we identified Cullin5 (CUL5) and suppressor of cytokine signaling 3 (SOCS3), two components of the Cullin-RING E3 ubiquitin ligase complex, as top candidates. Mechanistically, the deficiency of CUL5 or SOCS3 disrupted the functional formation of the E3 ligase complex and prevented the degradation of integrin β1, which stabilized integrin β1 and activated downstream focal adhesion kinase/SRC (FAK/SRC) signaling and eventually drove SCLC metastasis.

Gossypol induces pyroptosis in mouse macrophages via a non-canonical inflammasome pathway.

Gossypol, a polyphenolic compound isolated from cottonseeds, has been reported to possess many pharmacological activities, but whether it can influence inflammasome activation remains unclear. In this study, we found that in mouse macrophages, gossypol induced cell death characterized by rapid membrane rupture and robust release of HMGB1 and pro-caspase-11 comparable to ATP treatment, suggesting an induction of pyroptotic cell death. Unlike ATP, gossypol induced much low levels of mature interleukin-1β (IL-1β) secretion from mouse peritoneal macrophages primed with LPS, although it caused pro-IL-1β release similar to that of ATP.

The BH3-mimetic gossypol and noncytotoxic doses of valproic acid induce apoptosis by suppressing cyclin-A2/Akt/FOXO3a signaling.

Previously we reported that valproic acid (VPA) acts in synergy with GOS to enhance cell death in human DU145 cells. However, the underlying mechanism remains elusive. In this study, we observed that such synergistic cytotoxicity of GOS and VPA could be extended to human A375, HeLa, and PC-3 cancer cells.

Piperine metabolically regulates peritoneal resident macrophages to potentiate their functions against bacterial infection.

Pepper, a daily-used seasoning for promoting appetite, is widely used in folk medicine for treating gastrointestinal diseases. Piperine is the major alkaloid in pepper and possesses a wide range of pharmacological activities. However, the mechanism for linking metabolic and medicinal activities of piperine remains unknown.

The critical molecular interconnections in regulating apoptosis and autophagy.

Apoptosis and autophagy are both highly regulated biological processes that have important roles in development, differentiation, homeostasis, and disease. These processes may take place independently, with autophagy being cytoprotective for preventing cells from apoptosis and apoptosis blocking autophagy. But in most circumstances, both may be induced sequentially with autophagy preceding apoptosis.

Cucurbitacin E Induces Autophagy via Downregulating mTORC1 Signaling and Upregulating AMPK Activity.

Cucurbitacins, the natural triterpenoids possessing many biological activities, have been reported to suppress the mTORC1/p70S6K pathway and to induce autophagy. However, the correlation between such activities is largely unknown. In this study, we addressed this issue in human cancer cells in response to cucurbitacin E (CuE) treatment.

Chloroquine differentially modulates inflammatory cytokine expression in RAW 264.7 cells in response to inactivated Staphylococcus aureus.

The anti-inflammatory property of chloroquine (CQ) has long been recognized. This study aimed to investigate the effect of CQ on proinflammatory cytokine expression in RAW 264.7 macrophages stimulated with heat-inactivated Staphylococcus aureus cells (SAC).