scholarly journals Current Development and Application of Anaerobic Glycolytic Enzymes in Urothelial Cancer

2021 ◽  
Vol 22 (19) ◽  
pp. 10612
Author(s):  
Yi-Fang Yang ◽  
Hao-Wen Chuang ◽  
Wei-Ting Kuo ◽  
Bo-Syuan Lin ◽  
Yu-Chan Chang
Keyword(s):  
Urothelial Cancer ◽  
Malignant Tumors ◽  
Genetic Alterations ◽  
Clinical Applications ◽  
Glycolytic Enzymes ◽  
Metabolic Reprogramming ◽  
Urinary System ◽  
Aberrant Expression ◽  
Genetic Changes ◽  
Upper Tract Urothelial Cancer

Urothelial cancer is a malignant tumor with metastatic ability and high mortality. Malignant tumors of the urinary system include upper tract urothelial cancer and bladder cancer. In addition to typical genetic alterations and epigenetic modifications, metabolism-related events also occur in urothelial cancer. This metabolic reprogramming includes aberrant expression levels of genes, metabolites, and associated networks and pathways. In this review, we summarize the dysfunctions of glycolytic enzymes in urothelial cancer and discuss the relevant phenotype and signal transduction. Moreover, we describe potential prognostic factors and risks to the survival of clinical cancer patients. More importantly, based on several available databases, we explore relationships between glycolytic enzymes and genetic changes or drug responses in urothelial cancer cells. Current advances in glycolysis-based inhibitors and their combinations are also discussed. Combining all of the evidence, we indicate their potential value for further research in basic science and clinical applications.

scholarly journals A Pan-cancer Analysis of the Prognostic and Immunological Role of PPP1R14A

2021 ◽  
Author(s):  
JiaJie Lu ◽  
Rihong Huang ◽  
Haojian Wang ◽  
Yuecheng Peng ◽  
Yongyang Fan ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Cancer Survival ◽  
Malignant Tumors ◽  
Genetic Alterations ◽  
Poor Overall Survival ◽  
Carcinogenic Effect ◽  
Genetic Changes ◽  
Pan Cancer

Abstract BackgroundDespite emerging evidence revealed the remarkable roles of Protein Phosphatase 1 Regulatory Inhibitor Subunit 14A (PPP1R14A) in cancer tumorigenesis and progression, no pan-cancer analysis is available. Our research, for the first time, comprehensively investigated the potential carcinogenic mechanism of PPP1R14A across 33 tumors using bioinformatic techniques. MethodsTCGA datasets and the CPTAC datasets embedded in UALCAN were first applied to study the differential expression of PPP1R14A in various cancer types at the transcription and protein levels, respectively. Besides, we also conducted relevant prognostic survival analysis and used the GEPIA2 database to explore the association between PPP1R14A expression and pathological stages. In addition, cBioPortal and UALCAN databases were employed to analyze the genetic alterations and post-transcriptional phosphorylation of PPP1R14A. Then based on TCGA, we analyzed the relationship between PPP1R14A and immune infiltration, the correlation with tumor mutational burden (TMB), microsatellite instability (MSI) and immune checkpoint molecules (ICMs), and whether it is expected to be a predictive indicator in cancer patients, which was achieved by receiver operating characteristic (ROC) curve. Finally, STRING, GEPIE2 and TIMER2.0 databased were used to explore the potential mechanism of PPP1R14A in cancer and find molecules that have potential close interactions with PPP1R14A.ResultsPPP1R14A is down-expressed in major malignancies and there is a significant correlation between the PPP1R14A expression and the prognosis of patients. Pan-cancer survival analysis indicated that the high expression of PPP1R14A in most cases was associated with poor overall survival (OS), disease-specific survival (DSS), and progress-free interval (PFI) across patients with various malignant tumors, containing adrenocortical carcinoma (ACC), bladder urothelial carcinoma (BLCA). The results of ROC analysis subsequently exhibited that the molecule has a high reference significance in diagnosing a variety of cancers. Besides, we detected that the frequency of PPP1R14A genetic changes including genetic mutations and copy number alterations (CNAs) in uterine carcinosarcoma reached 16.07%, and these alterations brought misfortune to the survival and prognosis of cancer patients. In addition, the methylation within the promoter region of PPP1R14A DNA was enhanced in a majority of cancers. Downregulated phosphorylation levels of phosphorylation sites including S26, T38, etc. in most cases took place in several tumors, such as breast cancer, colon cancer, etc. PPP1R14A remarkably correlated with the levels of infiltrating cells and immune checkpoint genes. ConclusionsOur research summarized and analyzed the carcinogenic effect of PPP1R14A in different tumors comprehensively and provided a theoretical basis for promising therapeutic and immunotherapy strategies.

scholarly journals Tumor Classification Should Be Based on Biology and Not Consensus: Re-Defining Tumors Based on Biology May Accelerate Progress, An Experience of Gastric Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3159
Author(s):  
Helge Waldum
Keyword(s):  
Gastric Cancer ◽  
Malignant Tumors ◽  
Growth Control ◽  
Neuroendocrine Differentiation ◽  
Diffuse Type ◽  
Cell Of Origin ◽  
Genetic Changes ◽  
Ecl Cell ◽  
Neuroendocrine Carcinomas ◽  
Complete Carcinogens

Malignant tumors are a consequence of genetic changes mainly occurring during cell division, sometimes with a congenital component. Therefore, accelerated cell divisions will necessarily predispose individuals, whether due to conditions of chronic cell destruction or hormonal overstimulation. It has been postulated that two genetic hits are necessary for the development of malignancy (Knudson). The correct view is probably that the number of genetic changes needed depends on the role the mutated genes have in proliferation and growth control. Hormones should accordingly be regarded as complete carcinogens. In this review based upon experience of gastric cancer where gastrin is central in the pathogenesis, it is argued that oxyntic atrophy—and not metaplasia as postulated by Correa—is the central precancer change in gastric mucosa. Moreover, the target cell of gastrin, the enterochromaffin-like (ECL) cell, is central in gastric carcinogenesis and most probably the cell of origin of gastric carcinomas of the diffuse type according to Lauren (a classification probable in accordance with biology). The distinction between adenocarcinomas and neuroendocrine carcinomas based upon a certain percentage of cancer cells with neuroendocrine differentiation is questioned. To make progress in the treatment of cancer, a correct classification system and knowledge of the pathogenesis are necessary.

scholarly journals Splicing factor USP39 promotes ovarian cancer malignancy through maintaining efficient splicing of oncogenic HMGA2

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Shourong Wang ◽  
Zixiang Wang ◽  
Jieyin Li ◽  
Junchao Qin ◽  
Jianping Song ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Malignant Tumors ◽  
Splicing Factor ◽  
Ovarian Cancer Cells ◽  
Nuclear Speckles ◽  
Aberrant Expression ◽  
Intergenic Regions

AbstractAberrant expression of splicing factors was found to promote tumorigenesis and the development of human malignant tumors. Nevertheless, the underlying mechanisms and functional relevance remain elusive. We here show that USP39, a component of the spliceosome, is frequently overexpressed in high-grade serous ovarian carcinoma (HGSOC) and that an elevated level of USP39 is associated with a poor prognosis. USP39 promotes proliferation/invasion in vitro and tumor growth in vivo. Importantly, USP39 was transcriptionally activated by the oncogene protein c-MYC in ovarian cancer cells. We further demonstrated that USP39 colocalizes with spliceosome components in nuclear speckles. Transcriptomic analysis revealed that USP39 deletion led to globally impaired splicing that is characterized by skipped exons and overrepresentation of introns and intergenic regions. Furthermore, RNA immunoprecipitation sequencing showed that USP39 preferentially binds to exon-intron regions near 5′ and 3′ splicing sites. In particular, USP39 facilitates efficient splicing of HMGA2 and thereby increases the malignancy of ovarian cancer cells. Taken together, our results indicate that USP39 functions as an oncogenic splicing factor in ovarian cancer and represents a potential target for ovarian cancer therapy.

Molecular subtypes of upper tract urothelial cancer: Setting the stage for precision therapy

Cancer Cell ◽  
2021 ◽  
Vol 39 (6) ◽  
pp. 745-747
Author(s):  
David J. McConkey ◽  
Nirmish Singla ◽  
Phillip Pierorazio ◽  
Kara Lombardo ◽  
Andres Matoso ◽  
...  
Keyword(s):  
Urothelial Cancer ◽  
Molecular Subtypes ◽  
Upper Tract ◽  
Precision Therapy ◽  
Upper Tract Urothelial Cancer ◽  
Cancer Setting

scholarly journals Metabolic Reprogramming by Reduced Calorie Intake or Pharmacological Caloric Restriction Mimetics for Improved Cancer Immunotherapy

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1260
Author(s):  
Erwan Eriau ◽  
Juliette Paillet ◽  
Guido Kroemer ◽  
Jonathan G. Pol
Keyword(s):  
Clinical Trials ◽  
Caloric Restriction ◽  
Malignant Tumors ◽  
Checkpoint Inhibitors ◽  
Metabolic Reprogramming ◽  
Therapeutic Interventions ◽  
Model Organisms ◽  
Calorie Intake ◽  
Multiple Model ◽  
Autophagy Induction

Caloric restriction and fasting have been known for a long time for their health- and life-span promoting effects, with coherent observations in multiple model organisms as well as epidemiological and clinical studies. This holds particularly true for cancer. The health-promoting effects of caloric restriction and fasting are mediated at least partly through their cellular effects—chiefly autophagy induction—rather than reduced calorie intake per se. Interestingly, caloric restriction has a differential impact on cancer and healthy cells, due to the atypical metabolic profile of malignant tumors. Caloric restriction mimetics are non-toxic compounds able to mimic the biochemical and physiological effects of caloric restriction including autophagy induction. Caloric restriction and its mimetics induce autophagy to improve the efficacy of some cancer treatments that induce immunogenic cell death (ICD), a type of cellular demise that eventually elicits adaptive antitumor immunity. Caloric restriction and its mimetics also enhance the therapeutic efficacy of chemo-immunotherapies combining ICD-inducing agents with immune checkpoint inhibitors targeting PD-1. Collectively, preclinical data encourage the application of caloric restriction and its mimetics as an adjuvant to immunotherapies. This recommendation is subject to confirmation in additional experimental settings and in clinical trials. In this work, we review the preclinical and clinical evidence in favor of such therapeutic interventions before listing ongoing clinical trials that will shed some light on this subject.

Salivary Duct Carcinoma With Rhabdoid Features—No or Aberrant Expression of E-cadherin and Genetic Changes in CDH1

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Kimihide Kusafuka ◽  
Hidetaka Yamada ◽  
Keiko Ishino ◽  
Matsuyoshi Maeda ◽  
Koji Yamanegi ◽  
...  
Keyword(s):  
Salivary Duct Carcinoma ◽  
Salivary Duct ◽  
Aberrant Expression ◽  
Duct Carcinoma ◽  
Genetic Changes ◽  
Rhabdoid Features ◽  
E Cadherin
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