DGAT1 Inhibition Enhances Olaparib-Induced Lipotoxic Apoptosis in Metastatic Castration-Resistant Prostate Cancer.

Despite the initial success of poly (ADP-ribose) polymerase (PARP) inhibitors, achieving durable responses and effective treatment outcomes in metastatic castration-resistant prostate cancer (mCRPC) remains challenging. Resistance to the PARP inhibitor Olaparib is primarily mediated by the induction of autophagy, which enhances the availability of free fatty acids (FFA). Cancer cells mitigate the toxic effects of excessive lipid accumulation by sequestering FFA into lipid droplets (LD) through diacylglycerol O-acyltransferase 1 (DGAT1)-mediated lipid storage.

PROX1 is an early driver of lineage plasticity in prostate cancer.

Lineage plasticity is recognized as a critical determinant of lethality and resistance to AR pathway inhibitors in prostate cancer. Lineage plasticity is a continuum, ranging from AR activity-low tumors, AR-null tumors that do not express a neuroendocrine prostate cancer (NEPC) program (i.e.

Fibronectin-dependent integrin signaling drives EphA2 expression in vascular smooth muscle cells.

Vascular smooth muscle cells undergo a phenotypic shift to a "synthetic" phenotype during atherosclerosis characterized by downregulation of contractile markers and augmented proliferation, migration, and extracellular matrix deposition. While absent in contractile smooth muscle cells, the receptor tyrosine kinase EphA2 shows enhanced expression in synthetic vascular smooth muscle in vitro and in atherosclerotic plaques in vivo. EphA2 deletion in atheroprone knockout mice reduces plaque size, fibrous tissue, and smooth muscle content.

Wnt/Beta-Catenin Signaling Is Active in Neuroendocrine Prostate Cancer.

Wnt/beta-Catenin signaling plays a critical role in prostate cancer (PCa) progression, yet its precise contributions in neuroendocrine prostate cancer (NEPCa) remain incompletely understood. In this study, we utilized TRAMP/Wnt-reporter mice to monitor Wnt/beta-Catenin activity and investigated transcriptional alterations associated with NEPCa development. RNA sequencing and pathway enrichment analyses identified neuroactive ligand-receptor interaction, MAPK, calcium, and cAMP signaling as key pathways enriched in NEPCa.

Androgen Deprivation-Induced TET2 Activation Fuels Prostate Cancer Progression via Epigenetic Priming and Slow-Cycling Cancer Cells.

Advanced prostate cancer (PCa) frequently develops resistance to androgen deprivation therapy through various mechanisms including lineage plasticity. Slow-cycling cells (SCCs) have emerged as key players in adaptive responses to therapy, yet their role in PCa remains unclear. Through in silico analysis of single-cell RNA sequencing (scRNA-seq) data, we discovered that SCCs are enriched during pivotal stages of PCa progression, including the transition from androgen-dependent to castration-resistant states and the emergence of neuroendocrine PCa (NEPC).

Systematic multi-omics investigation of androgen receptor driven gene expression and epigenetics changes in prostate cancer.

Background: Prostate cancer, a common malignancy, is driven by androgen receptor (AR) signaling. Understanding the function of AR signaling is critical for prostate cancer research.

Methods: We performed multi-omics data analysis for the AR, androgen-sensitive LNCaP cell line, focusing on gene expression (RNAseq), chromatin accessibility (ATACseq), and transcription factor binding (ChIPseq).

Stathmin 1 expression in neuroendocrine and proliferating prostate cancer.

Prostate cancer (PCa) is the second leading cause of cancer-related mortality among men in the United States. While PCa initially responds to androgen deprivation therapy, a significant portion progresses to castration-resistant PCa. Approximately 20-25% of these cases acquire aggressive neuroendocrine (NE) features, ultimately leading to neuroendocrine prostate cancer (NEPC).

Stathmin 1 Expression in Neuroendocrine and Proliferating Prostate Cancer.

Prostate cancer (PCa) is the second leading cause of cancer-related mortality among men in the United States. While PCa initially responds to androgen deprivation therapy, a significant portion progresses to castration-resistant PCa. Approximately 20-25% of these cases acquire aggressive neuroendocrine (NE) features, ultimately leading to neuroendocrine prostate cancer (NEPC).

Transcriptomic analysis of melanoma cells reveals an association of α-synuclein with regulation of the inflammatory response.

The Parkinson's disease protein, alpha-synuclein (α-syn/SNCA), is highly expressed in neurons and melanomas. The goal of this study was to reveal the mechanism(s) of α-syn's involvement in melanoma pathogenesis. To decipher the genes and pathways affected by α-syn, we conducted an RNA sequencing analysis of human SK-MEL-28 cells and several SK-MEL-28 SNCA-KO clones.

Unveiling novel double-negative prostate cancer subtypes through single-cell RNA sequencing analysis.

Recent advancements in single-cell RNA sequencing (scRNAseq) have facilitated the discovery of previously unrecognized subtypes within prostate cancer (PCa), offering new insights into cancer heterogeneity and progression. In this study, we integrated scRNAseq data from multiple studies, comprising publicly available cohorts and data generated by our research team, and established the Human Prostate Single cell Atlas (HuPSA) and Mouse Prostate Single cell Atlas (MoPSA) datasets. Through comprehensive analysis, we identified two novel double-negative PCa populations: KRT7 cells characterized by elevated KRT7 expression and progenitor-like cells marked by SOX2 and FOXA2 expression, distinct from NEPCa, and displaying stem/progenitor features.

Systematic Multi-Omics Investigation of Androgen Receptor Driven Gene Expression and Epigenetics changes in Prostate Cancer.

Background: Prostate cancer, a common malignancy, is driven by androgen receptor (AR) signaling. Understanding the function of AR signaling is critical for prostate cancer research.

Methods: We performed multi-omics data analysis for the AR, androgen-sensitive LNCaP cell line, focusing on gene expression (RNAseq), chromatin accessibility (ATACseq), and transcription factor binding (ChIPseq).

Unveiling Novel Double-Negative Prostate Cancer Subtypes Through Single-Cell RNA Sequencing Analysis.

Recent advancements in single-cell RNA sequencing (scRNAseq) have facilitated the discovery of previously unrecognized subtypes within prostate cancer (PCa), offering new insights into disease heterogeneity and progression. In this study, we integrated scRNAseq data from multiple studies, comprising both publicly available cohorts and data generated by our research team, and established the HuPSA (Human Prostate Single cell Atlas) and the MoPSA (Mouse Prostate Single cell Atlas) datasets. Through comprehensive analysis, we identified two novel double-negative PCa populations: KRT7 cells characterized by elevated KRT7 expression, and progenitor-like cells marked by SOX2 and FOXA2 expression, distinct from NEPCa, and displaying stem/progenitor features.

The expression of PKM1 and PKM2 in developing, benign, and cancerous prostatic tissues.

Background: Neuroendocrine prostate cancer (NEPCa) is the most aggressive type of prostate cancer (PCa). However, energy metabolism, one of the hallmarks of cancer, in NEPCa has not been well studied. Pyruvate kinase M (PKM), which catalyzes the final step of glycolysis, has two main splicing isoforms, PKM1 and PKM2.

PCTA, a pan-cancer cell line transcriptome atlas.

A substantial volume of RNA sequencing data have been generated from cancer cell lines. However, it requires specific bioinformatics skills to compare gene expression levels across cell lines. This has hindered non-bioinformaticians from fully utilizing these valuable datasets in their research.

PCTA, A PAN-CANCER CELL LINE TRANSCRIPTOME ATLAS.

Background: A substantial volume of RNA sequencing data were generated from cancer cell lines. However, it requires specific bioinformatics skills to compare gene expression levels across cell lines. This has hindered non-bioinformaticians from fully utilizing these valuable datasets in their research.

The expression of PKM1 and PKM2 in developing, benign, and cancerous prostatic tissues.

Neuroendocrine prostate cancer (NEPCa) is the most aggressive type of prostate cancer. However, energy metabolism, one of the hallmarks of cancer, in NEPCa has not been well studied. Pyruvate kinase M (PKM), which catalyzes the final step of glycolysis, has two main splicing isoforms, PKM1 and PKM2.

Exploiting TLK1 and Cisplatin Synergy for Synthetic Lethality in Androgen-Insensitive Prostate Cancer.

Cellular organisms possess intricate DNA damage repair and tolerance pathways to manage various DNA lesions arising from endogenous or exogenous sources. The dysregulation of these pathways is associated with cancer development and progression. Synthetic lethality (SL), a promising cancer therapy concept, involves exploiting the simultaneous functional loss of two genes for selective cell death.

The interleukin-1 receptor type-1 in disturbed flow-induced endothelial mesenchymal activation.

Introduction: Atherosclerosis is a progressive disease that develops in areas of disturbed flow (d-flow). Progressive atherosclerosis is characterized by bulky plaques rich in mesenchymal cells and high-grade inflammation that can rupture leading to sudden cardiac death or acute myocardial infarction. In response to d-flow, endothelial cells acquire a mesenchymal phenotype through endothelial-to-mesenchymal transition (EndMT).

Alteration of Cellular Energy Metabolism through LPAR2-Axin2 Axis in Gastric Cancer.

Lysophosphatidic acid (LPA), a multifunctional endogenous phospholipid, plays a vital role in cellular homeostasis and the malignant behavior of cancer cells through G-protein-coupled receptors. However, the role of LPA in β-catenin-mediated gastric cancer is unknown. Here, we have noted the high expression of LPAR2 in human gastric cancer tissues, and that LPA treatment significantly increased the proliferation, migration, and invasion of human gastric cancer cells.

CTPC, a combined transcriptome data set of human prostate cancer cell lines.

Background: Cell lines are the most used model system in cancer research. The transcriptomic data of established prostate cancer (PCa) cell lines help researchers explore differential gene expressions across the various PCa cell lines.

Methods: Through large scale datamining, we established a curated Combined Transcriptome dataset of PCa Cell lines (CTPC) which contains the transcriptomic data of 1840 samples of 9 commonly used PCa cell lines including LNCaP, LNCaP-95, LNCaP-abl, C4-2, VCaP, 22Rv1, PC3, DU145, and NCI-H660.

Knocking out alpha-synuclein in melanoma cells dysregulates cellular iron metabolism and suppresses tumor growth.

The protein alpha-synuclein (α-syn) is unusual because, depending on its conformation and the type of cell in which it is expressed, it is pro-death or pro-survival, triggering neurodegeneration in Parkinson's disease and enhancing cell survival of some melanomas. To probe the function of α-syn in melanoma, we used CRISPR/Cas9 to knockout SNCA, the gene that codes for α-syn, in SK-Mel-28 melanoma cells. The SNCA-knockout clones in culture exhibited a decrease in the transferrin receptor 1 (TfR1), an increase in ferritin, an increase of reactive oxygen species and proliferated slower than control cells.

Neuroendocrine prostate cancer has distinctive, non-prostatic HOX code that is represented by the loss of HOXB13 expression.

HOX gene-encoded homeobox proteins control body patterning during embryonic development; the specific expression pattern of HOX genes may correspond to tissue identity. In this study, using RNAseq data of 1019 human cancer cell lines that originated from 24 different anatomic sites, we established HOX codes for various types of tissues. We applied these HOX codes to the transcriptomic profiles of prostate cancer (PCa) samples and found that the majority of prostate adenocarcinoma (AdPCa) samples sustained a prostate-specific HOX code whereas the majority of neuroendocrine prostate cancer (NEPCa) samples did not, which reflects the anaplastic nature of NEPCa.