Transcriptome-aligned metabolic profiling by SERSome reflects biological changes following mesenchymal stem cells expansion.

Background: Mesenchymal stem cells (MSCs) are widely applied in the treatment of various clinical diseases and in the field of medical aesthetics. However, MSCs exhibit greater heterogeneity limited stability, and more complex molecular and mechanistic characteristics compared to conventional drugs, making rapid and precise monitoring more challenging.

Methods: Surface-enhanced Raman spectroscopy (SERS) is an ultrasensitive, tractable and low-cost fingerprinting technique capable of identifying a wide range of molecules related to biological processes.

Epithelial NSD2 maintains FMO-mediated taurine biosynthesis to prevent intestinal barrier disruption.

Background: Inflammatory bowel disease (IBD) presents a significant challenge due to its intricate pathogenesis. NSD2, a histone methyltransferase responsible for dimethylating histone 3 at lysine 36, is associated with transcriptional activation. NSD2 expression is decreased in both the intestinal epithelial cells (IECs) of IBD patients and the IBD mouse model.

Targeting SOX4/PCK2 signaling suppresses neuroendocrine trans-differentiation of castration-resistant prostate cancer.

Background: Neuroendocrine prostate cancer (NEPC), a lethal subset of prostate cancer (PCa), is characterized by loss of AR signaling and resistance to AR-targeted therapy. While it is well reported that second-generation AR blockers induce neuroendocrine (NE) trans-differentiation of castration-resistant prostate cancer (CRPC) to promote the occurrence of NEPC, and pluripotent transcription factors might be potential regulators, the underlying molecular mechanisms remain unclear.

Methods: We analyzed the data from public databsets to screen candidate genes and then focused on SOX4, a regulator of NE trans-differentiation.

Multilevel Regulation of NF-κB Signaling by NSD2 Suppresses Kras-Driven Pancreatic Tumorigenesis.

Pancreatic ductal adenocarcinoma (PDAC) is a clinically challenging cancer with a dismal overall prognosis. NSD2 is an H3K36-specific di-methyltransferase that has been reported to play a crucial role in promoting tumorigenesis. Here, the study demonstrates that NSD2 acts as a putative tumor suppressor in Kras-driven pancreatic tumorigenesis.

Region-Specific CD16 Neutrophils Promote Colorectal Cancer Progression by Inhibiting Natural Killer Cells.

The colon is the largest compartment of the immune system, with innate immune cells exposed to antigens in the environment. However, the mechanisms by which the innate immune system is instigated are poorly defined in colorectal cancer (CRC). Here, a population of CD16 neutrophils that specifically accumulate in CRC tumor tissues by imaging mass cytometry (IMC), immune fluorescence, and flow cytometry, which demonstrated pro-tumor activity by disturbing natural killer (NK) cells are identified.

PAX6 promotes neuroendocrine phenotypes of prostate cancer via enhancing MET/STAT5A-mediated chromatin accessibility.

Background: Neuroendocrine prostate cancer (NEPC) is a lethal subset of prostate cancer which is characterized by neuroendocrine differentiation and loss of androgen receptor (AR) signaling. Growing evidence reveals that cell lineage plasticity is crucial in the failure of NEPC therapies. Although studies suggest the involvement of the neural transcription factor PAX6 in drug resistance, its specific role in NEPC remains unclear.

Zeb1-controlled metabolic plasticity enables remodeling of chromatin accessibility in the development of neuroendocrine prostate cancer.

Cell plasticity has been found to play a critical role in tumor progression and therapy resistance. However, our understanding of the characteristics and markers of plastic cellular states during cancer cell lineage transition remains limited. In this study, multi-omics analyses show that prostate cancer cells undergo an intermediate state marked by Zeb1 expression with epithelial-mesenchymal transition (EMT), stemness, and neuroendocrine features during the development of neuroendocrine prostate cancer (NEPC).

Uncovering impaired mitochondrial and lysosomal function in adipose-derived stem cells from obese individuals with altered biological activity.

Background: Adipose-derived stem cells (ADSCs) have been extensively used in preclinical and clinical trials for treating various diseases. However, the differences between ADSCs from lean individuals (L-ADSCs) and those from obese individuals (O-ADSCs) have not been thoroughly investigated, particularly regarding their mitochondrial and lysosomal functions. Therefore, this study aims to evaluate the differences between L-ADSCs and O-ADSCs in terms of cell biological activity, mitochondria, and lysosomes.

ADORA2A-driven proline synthesis triggers epigenetic reprogramming in neuroendocrine prostate and lung cancers.

Cell lineage plasticity is one of the major causes for the failure of targeted therapies in various cancers. However, the driver and actionable drug targets in promoting cancer cell lineage plasticity are scarcely identified. Here, we found that a G protein-coupled receptor, ADORA2A, is specifically upregulated during neuroendocrine differentiation, a common form of lineage plasticity in prostate cancer and lung cancer following targeted therapies.

Taurine Inhibits Ferroptosis Mediated by the Crosstalk between Tumor Cells and Tumor-Associated Macrophages in Prostate Cancer.

Tumor-associated macrophages (TAMs) play an essential role in tumor therapeutic resistance. Although the lethal effect of ferroptosis on tumor cells is well reported, how TAMs inhibit the effect of ferroptosis in tumors has not been clearly defined. In this study, it is demonstrated that TAM-secreted taurine suppresses ferroptosis in prostate cancer (PCa) by activating the Liver X receptor alpha/Stearoyl-Coenzyme A desaturase 1 (LXRα/SCD1) pathway.

hnRNPA2B1 promotes the occurrence and progression of hepatocellular carcinoma by downregulating PCK1 mRNA via a m6A RNA methylation manner.

Background: N6-methyladenosine (m6A) is the most prevalent RNA modification. Although hnRNPA2B1, as a reader of m6A modification, has been reported to promote tumorigenesis in a few types of tumors, its role in hepatocellular carcinoma (HCC) and the underlying molecular mechanism remains unclear.

Methods: Multiple public databases were used to analyze the expression of hnRNPA2B1 in HCC and its correlation with survival prognosis.

Comparative evaluation of antitumor effects of TNF superfamily costimulatory ligands delivered by mesenchymal stem cells.

Stimulation of costimulatory receptors serves as an alternative immunotherapeutic strategy other than checkpoint inhibition. However, systemic administration of the agonistic antibodies is associated with severe toxicities, which is one of the major obstacles for their clinical application. This study aimed to develop a mesenchymal stem cell (MSC)-based system for tumor-targeted delivery of TNF superfamily ligands and assess their potential in enhancing antitumor immunity.

SETD2 deficiency accelerates sphingomyelin accumulation and promotes the development of renal cancer.

Patients with polycystic kidney disease (PKD) encounter a high risk of clear cell renal cell carcinoma (ccRCC), a malignant tumor with dysregulated lipid metabolism. SET domain-containing 2 (SETD2) has been identified as an important tumor suppressor and an immunosuppressor in ccRCC. However, the role of SETD2 in ccRCC generation in PKD remains largely unexplored.

Loss of SETD2 aggravates colorectal cancer progression caused by SMAD4 deletion through the RAS/ERK signalling pathway.

Backgound: Colorectal cancer (CRC) is a complex, multistep disease that arises from the interplay genetic mutations and epigenetic alterations. The histone H3K36 trimethyltransferase SET domain-containing 2 (SETD2), as an epigenetic signalling molecule, has a 5% mutation rate in CRC. SETD2 expression is decreased in the development of human CRC and mice treated with Azoxymethane /Dextran sodium sulfate (AOM/DSS).

SETD2 deficiency promotes renal fibrosis through the TGF-β/Smad signalling pathway in the absence of VHL.

Background: Renal fibrosis is the final development pathway and the most common pathological manifestation of chronic kidney disease. Epigenetic alteration is a significant intrinsic factor contributing to the development of renal fibrosis. SET domain-containing 2 (SETD2) is the sole histone H3K36 trimethyltransferase, catalysing H3K36 trimethylation.

Setd2 deficiency promotes gastric tumorigenesis through inhibiting the SIRT1/FOXO pathway.

Gastric cancer (GC) is the fifth most common cancer and the second leading cause of cancer death globally. SETD2 is a histone methyltransferase catalyzing tri-methylation of H3K36 (H3K36me3) and has been shown to participate in diverse biological processes and human tumors. However, the mechanism of SETD2 in GC remains unclear.

KDM6A promotes hepatocellular carcinoma progression and dictates lenvatinib efficacy by upregulating FGFR4 expression.

Background: Hepatocellular carcinoma (HCC) is one of the major causes of death from cancer and has a very poor prognosis with few effective therapeutic options. Despite the approval of lenvatinib for the treatment of patients suffering from advanced HCC, only a small number of patients can benefit from this targeted therapy.

Methods: Diethylnitrosamine (DEN)-CCL4 mouse liver tumour and the xenograft tumour models were used to evaluate the function of KDM6A in HCC progression.

An Early Neoplasia Index (ENI10), Based on Molecular Identity of CD10 Cells and Associated Stemness Biomarkers, is a Predictor of Patient Outcome in Many Cancers.

Unlabelled: An accurate estimate of patient survival at diagnosis is critical to plan efficient therapeutic options. A simple and multiapplication tool is needed to move forward the precision medicine era. Taking advantage of the broad and high CD10 expression in stem and cancers cells, we evaluated the molecular identity of aggressive cancer cells.

Histone methyltransferase KMT5C drives liver cancer progression and directs therapeutic response to PARP inhibitors.

Background And Aims: Epigenetic plasticity is a major challenge in cancer-targeted therapy. However, the molecular basis governing this process has not yet been clearly defined. Despite the considerable success of poly(ADP-ribose) polymerase inhibitors (PARPi) in cancer therapy, the limited response to PARPi, especially in HCC, has been a bottleneck in its clinical implications.

IL-1β Is an Androgen-Responsive Target in Macrophages for Immunotherapy of Prostate Cancer.

Great attention is paid to the role of androgen receptor (AR) as a central transcriptional factor in driving the growth of prostate cancer (PCa) epithelial cells. However, the understanding of the role of androgen in PCa-infiltrated immune cells and the impact of androgen deprivation therapy (ADT), the first-line treatment for advanced PCa, on the PCa immune microenvironment remains limited. On the other hand, immune checkpoint blockade has revolutionized the treatment of certain cancer types, but fails to achieve any benefit in advanced PCa, due to an immune suppressive environment.

Numb/Parkin-directed mitochondrial fitness governs cancer cell fate via metabolic regulation of histone lactylation.

Cell plasticity and neuroendocrine differentiation in prostate and lung adenocarcinomas are one of the major reasons for therapeutic resistance to targeted therapy. Whether and how metabolic changes contribute to this adenocarcinoma-to-neuroendocrine cell fate transition remains largely unclear. Here we show that neuroendocrine prostate or lung cancer cells possess mostly fragmented mitochondria with low membrane potential and rely on glycolysis for energy metabolism.

TRIM59 is suppressed by androgen receptor and acts to promote lineage plasticity and treatment-induced neuroendocrine differentiation in prostate cancer.

The incidence of treatment-induced neuroendocrine prostate cancer (t-NEPC) has been greatly increasing after the usage of secondgeneration androgen receptor (AR) pathway inhibitors (ARPIs). Neuroendocrine differentiation (NED) is closely associated with ARPI treatment failure and poor prognosis in prostate cancer (PCa) patients. However, the molecular mechanisms of NED are not fully understood.