DHRS2-induced SPHK1 downregulation contributes to the cell growth inhibition by Trichothecin in colorectal carcinoma.

Background: Deregulation of lipid metabolism is one of the most prominent metabolic features in cancer. The activation of sphingolipid metabolic pathways affects the proliferation, invasion, angiogenesis, chemoresistance, and immune escape of tumors, including colorectal cancer (CRC). Dehydrogenase/reductase member 2 (DHRS2), which belongs to the short-chain dehydrogenase/reductase (SDR) family, has been reported to participate in the regulation of lipid metabolism and impact on cancer progression.

Unlocking the potential: Targeting metabolic pathways in the tumor microenvironment for Cancer therapy.

Cancer incidence and mortality are increasing and impacting global life expectancy. Metabolic reprogramming in the tumor microenvironment (TME) is intimately related to tumorigenesis, progression, metastasis and drug resistance. Tumor cells drive metabolic reprogramming of other cells in the TME through metabolic induction of cytokines and metabolites, and metabolic substrate competition.

The role of novel protein acylations in cancer.

Novel protein acylations are a class of protein post-translational modifications, such as lactylation, succinylation, crotonylation, palmitoylation, and β-hydroxybutyrylation. These acylation modifications are common in prokaryotes and eukaryotes and play pivotal roles in various key cellular processes by regulating gene transcription, protein subcellular localization, stability and activity, protein-protein interactions, and protein-DNA interactions. The diversified acylations are closely associated with various human diseases, especially cancer.

The role of circadian gene CLOCK in cancer.

Circadian Locomotor Output Cycles Kaput (CLOCK) is one of the circadian clock genes and is considered to be a fundamental regulatory gene in the circadian rhythm, responsible for mediating several biological processes. Therefore, abnormal expression of CLOCK affects its role in the circadian clock and its more general function as a direct regulator of gene expression. This dysfunction can lead to severe pathological effects, including cancer.

Inhibition of UV-Induced Stress Signaling and Inflammatory Responses in SKH-1 Mouse Skin by Topical Small-Molecule PD-L1 Blockade.

The immune checkpoint ligand PD-L1 has emerged as a molecular target for skin cancer therapy and might also hold promise for preventive intervention targeting solar UV light-induced skin damage. In this study, we have explored the role of PD-L1 in acute keratinocytic photodamage testing the effects of small-molecule pharmacological inhibition. Epidermal PD-L1 upregulation in response to chronic photodamage was established using immunohistochemical and proteomic analyses of a human skin cohort, consistent with earlier observations that PD-L1 is upregulated in cutaneous squamous cell carcinoma.

CYLD induces high oxidative stress and DNA damage through class I HDACs to promote radiosensitivity in nasopharyngeal carcinoma.

Abnormal expression of Cylindromatosis (CYLD), a tumor suppressor molecule, plays an important role in tumor development and treatment. In this work, we found that CYLD binds to class I histone deacetylases (HDAC1 and HDAC2) through its N-terminal domain and inhibits HDAC1 activity. RNA sequencing showed that CYLD-HDAC axis regulates cellular antioxidant response via Nrf2 and its target genes.

Metabolic reprogramming in nasopharyngeal carcinoma: Mechanisms and therapeutic opportunities.

The high prevalence of metabolic reprogramming in nasopharyngeal carcinoma (NPC) offers an abundance of potential therapeutic targets. This review delves into the distinct mechanisms underlying metabolic reprogramming in NPC, including enhanced glycolysis, nucleotide synthesis, and lipid metabolism. All of these changes are modulated by Epstein-Barr virus (EBV) infection, hypoxia, and tumor microenvironment.

Comprehensive Physicochemical Characterization, In Vitro Membrane Permeation, and In Vitro Human Skin Cell Culture of a Novel TOPK Inhibitor, HI-TOPK-032.

Nonmelanoma skin cancers (NMSC) are the most common skin cancers, and about 5.4 million people are diagnosed each year in the United States. A newly developed T-lymphokine-activated killer cell-originated protein kinase (TOPK) inhibitor, HI-TOPK-032, is effective in suppressing colon cancer cell growth, inducing the apoptosis of colon cancer cells and ultraviolet (UV) light-induced squamous cell carcinoma (SCC).

Fyn-mediated phosphorylation of Menin disrupts telomere maintenance in stem cells.

Telomeres protect chromosome ends and determine the replication potential of dividing cells. The canonical telomere sequence TTAGGG is synthesized by telomerase holoenzyme, which maintains telomere length in proliferative stem cells. Although the core components of telomerase are well-defined, mechanisms of telomerase regulation are still under investigation.

Recent Advances in Carcinogenesis Transcription Factors: Biomarkers and Targeted Therapies.

Carcinogenesis, the process by which normal cells transform into cancer cells, is complex and multifaceted [...

Anoikis resistance and immune escape mediated by Epstein-Barr virus-encoded latent membrane protein 1-induced stabilization of PGC-1α promotes invasion and metastasis of nasopharyngeal carcinoma.

Background: Epstein-Barr virus (EBV) is the first discovered human tumor virus that is associated with a variety of malignancies of both lymphoid and epithelial origin including nasopharyngeal carcinoma (NPC). The EBV-encoded latent membrane protein 1 (LMP1) has been well-defined as a potent oncogenic protein, which is intimately correlated with NPC pathogenesis. Anoikis is considered to be a physiological barrier to metastasis, and avoiding anoikis is a major hallmark of metastasis.

Targeting CDK1 in cancer: mechanisms and implications.

Cyclin dependent kinases (CDKs) are serine/threonine kinases that are proposed as promising candidate targets for cancer treatment. These proteins complexed with cyclins play a critical role in cell cycle progression. Most CDKs demonstrate substantially higher expression in cancer tissues compared with normal tissues and, according to the TCGA database, correlate with survival rate in multiple cancer types.

Innovative Rocuronium Bromide Topical Formulation for Targeted Skin Drug Delivery: Design, Comprehensive Characterization, In Vitro 2D/3D Human Cell Culture and Permeation.

Cutaneous squamous cell carcinoma (cSCC) is the second-most common type of non-melanoma skin cancer and is linked to long-term exposure to ultraviolet (UV) radiation from the sun. Rocuronium bromide (RocBr) is an FDA-approved drug that targets p53-related protein kinase (PRPK) that inhibits the development of UV-induced cSCC. This study aimed to investigate the physicochemical properties and in vitro behavior of RocBr.

Endometriosis: Cell Death and Cell Signaling Machinery.

Endometriosis is an estrogen-dependent disorder defined as the deposition and growth of endometrial tissue outside the uterus, including but not limited to the pelvic peritoneum, rectovaginal septum, and ovaries. Endometriosis is a substantial contributor to pelvic pain and subfertility and has been associated with an increased incidence of certain cancers, including ovarian. Appropriate treatment of endometriosis can reduce morbidity, but generally is used only to address symptoms, since no cure currently exists.

DHRS2 inhibits cell growth and metastasis in ovarian cancer by downregulation of CHKα to disrupt choline metabolism.

The short-chain dehydrogenase/reductase (SDR) superfamily has essential roles in lipid metabolism and redox sensing. In recent years, accumulating evidence highlights the emerging association between SDR family enzymes and cancer. Dehydrogenase/reductase member 2(DHRS2) belongs to the NADH/NADPH-dependent SDR family, and extensively participates in the regulation of the proliferation, migration, and chemoresistance of cancer cells.

The emerging roles of HDACs and their therapeutic implications in cancer.

Deregulation of protein post-translational modifications is intensively involved in the etiology of diseases, including degenerative diseases, inflammatory injuries, and cancers. Acetylation is one of the most common post-translational modifications of proteins, and the acetylation levels are controlled by two mutually antagonistic enzyme families, histone acetyl transferases (HATs) and histone deacetylases (HDACs). HATs loosen the chromatin structure by neutralizing the positive charge of lysine residues of histones; whereas HDACs deacetylate certain histones, thus inhibiting gene transcription.

Erratum: Targeting Epstein-Barr virus oncoprotein LMP1-mediated high oxidative stress suppresses EBV lytic reactivation and sensitizes tumors to radiation therapy: Erratum.

[This corrects the article DOI: 10.7150/thno.46006.

CPT1A-mediated fatty acid oxidation promotes cell proliferation via nucleoside metabolism in nasopharyngeal carcinoma.

As the first rate-limiting enzyme in fatty acid oxidation (FAO), CPT1 plays a significant role in metabolic adaptation in cancer pathogenesis. FAO provides an alternative energy supply for cancer cells and is required for cancer cell survival. Given the high proliferation rate of cancer cells, nucleotide synthesis gains prominence in rapidly proliferating cells.

Prostaglandin Pathways: Opportunities for Cancer Prevention and Therapy.

Because of profound effects observed in carcinogenesis, prostaglandins (PG), prostaglandin-endoperoxide synthases, and PG receptors are implicated in cancer development and progression. Understanding the molecular mechanisms of PG actions has potential clinical relevance for cancer prevention and therapy. This review focuses on the current status of PG signaling pathways in modulating cancer progression and aims to provide insights into the mechanistic actions of PGs and their receptors in influencing tumor progression.

Mitochondria-Shaping Proteins and Chemotherapy.

The emergence, in recent decades, of an entirely new area of "Mitochondrial dynamics", which consists principally of fission and fusion, reflects the recognition that mitochondria play a significant role in human tumorigenesis and response to therapeutics. Proteins that determine mitochondrial dynamics are referred to as "shaping proteins". Marked heterogeneity has been observed in the response of tumor cells to chemotherapy, which is associated with imbalances in mitochondrial dynamics and function leading to adaptive and acquired resistance to chemotherapeutic agents.

Conformational change of adenine nucleotide translocase-1 mediates cisplatin resistance induced by EBV-LMP1.

Adenine nucleotide translocase-1 (ANT1) is an ADP/ATP transporter protein located in the inner mitochondrial membrane. ANT1 is involved not only in the processes of ADP/ATP exchange but also in the composition of the mitochondrial membrane permeability transition pore (mPTP); and the function of ANT1 is closely related to its own conformational changes. Notably, various viral proteins can interact directly with ANT1 to influence mitochondrial membrane potential by regulating the opening of mPTP, thereby affecting tumor cell fate.

ACSL family: The regulatory mechanisms and therapeutic implications in cancer.

Accumulating evidence shows that deregulation of fatty acid (FA) metabolism is associated with the development of cancer. Long-chain acyl-coenzyme A synthases (ACSLs) are responsible for activating long-chain FAs and are frequently deregulated in cancers. Among the five mammalian ACSL family members, ACSL1 is involved in the TNFα-mediated pro-inflammatory phenotype and mainly facilitates cancer progression.

Roles of regulator of chromosome condensation 2 in cancer: Beyond its regulatory function in cell cycle.

Regulator of chromosome condensation 2 (RCC2) is an essential protein in order for mitosis to proceed properly. It localizes in the centrosome of chromosomes where is involved in chromosome segregation and cytokinesis. Furthermore, RCC2 associates with integrin networks at the plasma membrane where participates in the control of cell movement.

Stabilization of p18 by deubiquitylase CYLD is pivotal for cell cycle progression and viral replication.

p18 is a key negative regulator of cell cycle progression and mediates cell cycle arrest at the G1/S phase. Ubiquitination is the prime mechanism in regulating p18 protein abundance. However, so far no post- translational regulator, especially DUBs, has been identified to regulate the protein stability of p18.