Ubiquitin-specific protease 7 maintains c-Myc stability to support pancreatic cancer glycolysis and tumor growth.

Background: The typical pathological feature of pancreatic ductal adenocarcinoma (PDAC) is a significant increase in stromal reaction, leading to a hypoxic and poorly vascularized tumor microenvironment. Tumor cells undergo metabolic reprogramming, such as the Warburg effect, yet the underlying mechanisms are not fully understood.

Methods: Interference and overexpression experiments were conducted to analyze the in vivo and in vitro effects of USP7 on the growth and glycolysis of tumor cells.

ITGA3 promotes pancreatic cancer progression through HIF1α- and c-Myc-driven glycolysis in a collagen I-dependent autocrine manner.

Pancreatic cancer is characterized by severe metabolic stress due to its prominent desmoplasia and poor vascularization. Integrin subunit alpha 3 (ITGA3) is a cell surface adhesion protein involved in tumor progression. However, the role of ITGA3 in pancreatic cancer progression, especially in metabolic reprogramming, remains largely unknown.

Natural products: promising therapeutics for targeting regulatory immune cells in the tumor microenvironment.

Regulatory immune cells regulate immune responses through various mechanisms, affecting the occurrence, development, and therapeutic effects of tumors. In this article, we reviewed the important roles of regulatory immune cells, such as regulatory T cells (Tregs), regulatory B cells (Bregs), myeloid-derived suppressor cells (MDSCs), regulatory dendritic cells (DCregs), and tumor-associated macrophages (TAMs), in the tumor microenvironment (TME). The immunomodulatory effects of natural products, such as polysaccharides, polyphenols, glycosides, alkaloids, terpenoids, quinones, and other compounds, which affect the functions of regulatory immune cells through molecular signaling pathways, thereby enhancing the potential of the antitumor immune response, are discussed.

A GAPDH serotonylation system couples CD8 T cell glycolytic metabolism to antitumor immunity.

Apart from the canonical serotonin (5-hydroxytryptamine [5-HT])-receptor signaling transduction pattern, 5-HT-involved post-translational serotonylation has recently been noted. Here, we report a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) serotonylation system that promotes the glycolytic metabolism and antitumor immune activity of CD8 T cells. Tissue transglutaminase 2 (TGM2) transfers 5-HT to GAPDH glutamine 262 and catalyzes the serotonylation reaction.

METTL3 suppresses pancreatic ductal adenocarcinoma progression through activating endogenous dsRNA-induced anti-tumor immunity.

Purpose: Although immunotherapy improves clinical outcomes in several types of malignancies, as an immunologically 'cold' tumor, pancreatic ductal adenocarcinoma (PDAC) is arrantly resistant to immunotherapy. However, the role of N6-methyladenosine (mA) modification in the immune microenvironment of PDAC is still poorly understood.

Methods: The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets were used to identify differentially expressed mA related enzymes.

PYGL-mediated glucose metabolism reprogramming promotes EMT phenotype and metastasis of pancreatic cancer.

Epithelial-mesenchymal transition (EMT) is closely associated with tumor invasion and metastasis. However, key regulators of EMT in pancreatic ductal adenocarcinoma (PDAC) need to be further studied. Bioinformatics analyses of pancreatic cancer public datasets showed that glycogen phosphorylase L (PYGL) expression is elevated in quasimesenchymal PDAC (QM-PDAC) and positively associated with EMT.

CXCR2 Is Essential for Radiation-Induced Intestinal Injury by Initiating Neutrophil Infiltration.

Neutrophils, known as an important part of the immune system, are the most abundant leukocyte population in peripheral blood, but excessive recruitment will lead to tissue/organ injury. RNA sequencing showed that ionizing radiation significantly increased the expression of characteristic genes of neutrophils in intestinal tissues compared with liver and lung tissues. By clearing neutrophils with an anti-Ly6G antibody, we found that neutrophil infiltration is critical for irradiation-induced intestinal injury.

ACSL4 is essential for radiation-induced intestinal injury by initiating ferroptosis.

Lipid peroxidation-induced ferroptosis is a newly recognized type of programmed cell death. With the method of RNA sequencing, we found that irradiation (IR) markedly increased the expression of ferroptosis promotive genes, whereas reduced the expression of ferroptosis suppressive genes in murine intestine tissues, when compared with those of liver and lung tissues. By using ferroptosis inducer RSL-3 and inhibitor liproxstatin-1, we found that ferroptosis is essential for IR-induced intestinal injury.

Targeting type Iγ phosphatidylinositol phosphate kinase overcomes oxaliplatin resistance in colorectal cancer.

Oxaliplatin is a widely used chemotherapy drug for advanced colorectal cancer (CRC) and its resistance is a major challenge for disease treatment. However, the molecular mechanism underlying oxaliplatin resistance remains largely elusive. An integrative analysis was performed to determine differentially expressed genes involved in oxaliplatin resistance.

Reciprocal regulation of LOXL2 and HIF1α drives the Warburg effect to support pancreatic cancer aggressiveness.

Hypoxic microenvironment is common in solid tumors, particularly in pancreatic ductal adenocarcinoma (PDAC). The Warburg effect is known to facilitate cancer aggressiveness and has long been linked to hypoxia, yet the underlying mechanism remains largely unknown. In this study, we identify that lysyl oxidase-like 2 (LOXL2) is a hypoxia-responsive gene and is essential for the Warburg effect in PDAC.

TRIM50 Suppresses Pancreatic Cancer Progression and Reverses the Epithelial-Mesenchymal Transition Facilitating the Ubiquitous Degradation of Snail1.

Emerging evidence suggests that the tripartite motif (TRIM) family play important roles in tumor development and progression. Tripartite motif-containing 50 (TRIM50) is a member of the TRIM family, but little is known regarding its expression and potential functional roles in cancer. In this study, we first analyzed the expression pattern and clinical significance of TRIM50 in pancreatic cancer and found that TRIM50 expression is significantly reduced in pancreatic cancer tissues and its downregulation is associated with poor survival for pancreatic cancer patients.

Targeting Purinergic Receptor P2RX1 Modulates Intestinal Microbiota and Alleviates Inflammation in Colitis.

Inflammatory bowel disease (IBD) remains one of the most prevalent gastrointestinal diseases worldwide. Purinergic signaling has emerged as a promising therapeutic target of inflammation-associated diseases. However, little is known about the specific roles of purinergic receptors in IBD.

Hypoxia-dependent expression of MAP17 coordinates the Warburg effect to tumor growth in hepatocellular carcinoma.

Background: Reprogrammed glucose metabolism, also known as the Warburg effect, which is essential for tumor progression, is regarded as a hallmark of cancer. MAP17, a small 17-kDa non-glycosylated membrane protein, is frequently dysregulated in human cancers. However, its role in hepatocellular carcinoma (HCC) remains largely unknown.

Deciphering the genomic and lncRNA landscapes of aerobic glycolysis identifies potential therapeutic targets in pancreatic cancer.

Aerobic glycolysis, also known as the Warburg effect, is emerged as a hallmark of most cancer cells. Increased aerobic glycolysis is closely associated with tumor aggressiveness and predicts a poor prognosis. Pancreatic ductal adenocarcinoma (PDAC) is characterized by prominent genomic aberrations and increased glycolytic phenotype.

TRIM59 predicts poor prognosis and promotes pancreatic cancer progression via the PI3K/AKT/mTOR-glycolysis signaling axis.

Aberrant expression of the tripartite motif containing 59 (TRIM59) has been reported to participate in the development and progression of various human cancers. However, its expression pattern and cellular roles in pancreatic cancer (PC) remains unclear. In our study, we found that TRIM59 expression was significantly increased in PC tissues and was positively correlated with several malignant behaviors and poor overall survival of PC patients based on bioinformatics analysis and immunohistochemistry staining.

GPAA1 promotes gastric cancer progression via upregulation of GPI-anchored protein and enhancement of ERBB signalling pathway.

Background: Gastric cancer is one of the deadliest malignant tumours, with a high incidence in China, and is regulated by aberrantly overexpressed oncogenes. However, existing therapies are insufficient to meet patients' needs; thus, the identification of additional therapeutic targets and exploration of the underlying mechanism are urgently needed. GPAA1 is the subunit of the GPI transamidase that transfers the GPI anchor to proteins within the ER.

GABRP regulates chemokine signalling, macrophage recruitment and tumour progression in pancreatic cancer through tuning KCNN4-mediated Ca signalling in a GABA-independent manner.

Background And Aims: Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death worldwide. Neurotransmitter-initiated signalling pathway is profoundly implicated in tumour initiation and progression. Here, we investigated whether dysregulated neurotransmitter receptors play a role during pancreatic tumourigenesis.

Exosome-mediated secretion of LOXL4 promotes hepatocellular carcinoma cell invasion and metastasis.

Background: Lysyl oxidase-like 4 (LOXL4) has been found to be dysregulated in several human malignancies, including hepatocellular carcinoma (HCC). However, the role of LOXL4 in HCC progression remains largely unclear. In this study, we investigated the clinical significance and biological involvement of LOXL4 in the progression of HCC.

Exemestane Attenuates Hepatic Fibrosis in Rats by Inhibiting Activation of Hepatic Stellate Cells and Promoting the Secretion of Interleukin 10.

Exemestane (EXE) is an irreversible steroidal aromatase inhibitor mainly used as an adjuvant endocrine therapy for postmenopausal women suffering from breast cancer. Besides inhibiting aromatase activity, EXE has multiple biological functions, such as antiproliferation, anti-inflammatory, and antioxidant activities which are all involved in hepatic fibrosis. Therefore, we investigated the role of EXE during the progress of hepatic fibrosis.

ITGBL1 Predicts a Poor Prognosis and Correlates EMT Phenotype in Gastric Cancer.

Integrin, beta-like 1 (ITGBL1), a β-integrin-related extracellular matrix protein, was found more commonly up-regulated in gastric cancer (GC) by screening and analyzing Gene Expression Omnibus (GEO) and Oncomine databases, reminding us to explore its prognostic significance in GC. In our current study, we observed that ITGBL1 expression was significantly up-regulated in GC compared with normal controls in clinical specimens. In addition, elevated ITGBL1 expression was positively correlated with patients' tumor-node-metastasis (TNM) stage and distant metastasis.

CCBE1 promotes GIST development through enhancing angiogenesis and mediating resistance to imatinib.

Gastrointestinal stromal tumor (GIST) is the most major mesenchymal neoplasm of the digestive tract. Up to now, imatinib mesylate has been used as a standard first-line treatment for irresectable and metastasized GIST patients or adjuvant treatment for advanced GIST patients who received surgical resection. However, secondary resistance to imatinib usually happens, resulting in a major obstacle in GIST successful therapy.

Trophoblast glycoprotein promotes pancreatic ductal adenocarcinoma cell metastasis through Wnt/planar cell polarity signaling.

Trophoblast glycoprotein (TPBG), a 72 kDa glycoprotein was identified using a monoclonal antibody, which specifically binds human trophoblast. The expression of TPBG in normal tissues is limited; however, it is upregulated in numerous types of cancer. When TPBG is expressed at a high level, this usually indicates a poor clinical outcome.

Silencing of WISP3 suppresses gastric cancer cell proliferation and metastasis and inhibits Wnt/β-catenin signaling.

CCN6/Wnt1-inducible signaling protein-3 (CCN6/WISP3) is a cysteine-rich protein that belongs to the CCN (Cyr61, CTGF, Nov) family of matricellular proteins, which are often dysregulated in cancers. However, the functional role and clinical significance of WISP3 in gastric cancer remain unclear. In this study, we found that silencing of WISP3 suppressed gastric cancer cell proliferation, migration and invasion.