Altered gene expression in glycolysis-cholesterol synthesis axis correlates with outcome of triple-negative breast cancer.

Published on Mar 1, 2021in Experimental Biology and Medicine3.139
· DOI :10.1177/1535370220975206
Peng-Cheng Zhong (Guangzhou University of Chinese Medicine), Rong Shu1
Estimated H-index: 1
(Guangzhou University of Chinese Medicine)
+ 3 AuthorsYing-Jie Hu6
Estimated H-index: 6
(Guangzhou University of Chinese Medicine)
#1Demin Cai (UC Davis: University of California, Davis)H-Index: 15
#1Demin Cai (UC Davis: University of California, Davis)H-Index: 3
Last. Hongwu Chen (UC Davis: University of California, Davis)H-Index: 39
view all 22 authors...
Tumor subtype-specific metabolic reprogrammers could serve as targets of therapeutic intervention. Here we show that triple-negative breast cancer (TNBC) exhibits a hyper-activated cholesterol-biosynthesis program that is strongly linked to nuclear receptor RORγ, compared to estrogen receptor-positive breast cancer. Genetic and pharmacological inhibition of RORγ reduces tumor cholesterol content and synthesis rate while preserving host cholesterol homeostasis. We demonstrate that RORγ functions ...
21 CitationsSource
#1Yang Li (Ha Tai: Xiamen University)H-Index: 7
#2Yan-Wei ShaH-Index: 12
Last. Zhongxian Lu (Ha Tai: Xiamen University)H-Index: 10
view all 16 authors...
: Multiple morphological abnormalities of flagella (MMAF) is one kind of severe teratozoospermia. Gene mutations reported in previous works only revealed the pathogenesis of approximately half of the MMAF cases, and more genetic defects in MMAF need to be explored. In the present study, we performed a genetic analysis on Han Chinese men with MMAF using whole-exome sequencing. After filtering out the cases with known gene mutations, we identified five novel mutation sites in the DNAH2 gene in thr...
20 CitationsSource
#1Ariadna Giro-Perafita (NYU: New York University)H-Index: 3
#2Marc Rabionet (University of Girona)H-Index: 8
Last. Teresa Puig (University of Girona)H-Index: 13
view all 7 authors...
Recent studies showed that Fatty Acid Synthase (FASN), a lipogenic enzyme overexpressed in several carcinomas, plays an important role in drug resistance. Furthermore, the enrichment of Breast Cancer Stem Cell (BCSC) features has been found in breast tumors that progressed after chemotherapy. Hence, we used the triple negative breast cancer (TNBC) cell line MDA-MB-231 (231) to evaluate the FASN and BCSC population role in resistance acquisition to chemotherapy. For this reason, parental cell lin...
8 CitationsSource
#1Ana C. Garrido-Castro (Harvard University)H-Index: 9
#2Nan Lin (Harvard University)H-Index: 93
Last. Kornelia Polyak (Harvard University)H-Index: 90
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Triple-negative breast cancer (TNBC) remains the most challenging breast cancer subtype to treat. To date, therapies directed to specific molecular targets have rarely achieved clinically meaningful improvements in outcomes of patients with TNBC, and chemotherapy remains the standard of care. Here, we seek to review the most recent efforts to classify TNBC based on the comprehensive profiling of tumors for cellular composition and molecular features. Technologic advances allow for tumor characte...
171 CitationsSource
#1Marc Poirot (University of Toulouse)H-Index: 33
#2Regis Soules (University of Toulouse)H-Index: 4
Last. Sandrine Silvente-Poirot (University of Toulouse)H-Index: 35
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Abstract Oxygenation products of cholesterol, named oxysterols, were suspected since the 20th century to be involved in carcinogenesis. Among the family of oxysterol molecules, cholesterol-5,6-epoxides (5,6-EC) retained the attention of scientists because they contain a putative alkylating epoxide group. However, studies failed into demonstrating that 5,6-EC were direct carcinogens and revealed a surprising chemical stability and unreactivity towards nucleophiles in standard conditions. Analyses...
5 CitationsSource
#1Mihriban Karaayvaz (Harvard University)H-Index: 8
#2Simona Cristea (Harvard University)H-Index: 8
Last. Leif W. Ellisen (Harvard University)H-Index: 52
view all 10 authors...
Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by extensive intratumoral heterogeneity. To investigate the underlying biology, we conducted single-cell RNA-sequencing (scRNA-seq) of >1500 cells from six primary TNBC. Here, we show that intercellular heterogeneity of gene expression programs within each tumor is variable and largely correlates with clonality of inferred genomic copy number changes, suggesting that genotype drives the gene expression phenotype of indiv...
121 CitationsSource
#1Philippe Icard (UNICAEN: University of Caen Lower Normandy)H-Index: 10
#2Seth ShulmanH-Index: 1
Last. Hubert Lincet (French Institute of Health and Medical Research)H-Index: 7
view all 6 authors...
Abstract Cancer cells employ both conventional oxidative metabolism and glycolytic anaerobic metabolism. However, their proliferation is marked by a shift towards increasing glycolytic metabolism even in the presence of O 2 (Warburg effect). HIF1, a major hypoxia induced transcription factor, promotes a dissociation between glycolysis and the tricarboxylic acid cycle, a process limiting the efficient production of ATP and citrate which otherwise would arrest glycolysis. The Warburg effect also f...
90 CitationsSource
#1Isabel EchavarriaH-Index: 5
Last. Miguel Martin (Complutense University of Madrid)H-Index: 62
view all 22 authors...
Purpose: Triple-negative breast cancer (TNBC) requires the iden- tification of reliable predictors of response to neoadjuvant chemotherapy (NACT). For this purpose, we aimed to evaluate the performance of the TNBCtype-4 classifier in a cohort of patients with TNBC treated with neoadjuvant carboplatin and docetaxel (TCb). Methods: Patients with TNBC were accrued in a nonrandomized trial of neoadjuvant carboplatin AUC 6 and docetaxel 75 mg/m 2 for six cycles. Response was evaluated in terms of pat...
26 CitationsSource
#1Xinxin Peng (University of Texas MD Anderson Cancer Center)H-Index: 13
#2Zhongyuan Chen (Rice University)H-Index: 4
Last. Oliver F. Bathe (U of C: University of Calgary)H-Index: 35
view all 21 authors...
Summary Metabolic reprogramming provides critical information for clinical oncology. Using molecular data of 9,125 patient samples from The Cancer Genome Atlas, we identified tumor subtypes in 33 cancer types based on mRNA expression patterns of seven major metabolic processes and assessed their clinical relevance. Our metabolic expression subtypes correlated extensively with clinical outcome: subtypes with upregulated carbohydrate, nucleotide, and vitamin/cofactor metabolism most consistently c...
59 CitationsSource
#1Yacine Bareche (ULB: Université libre de Bruxelles)H-Index: 9
#2David Venet (ULB: Université libre de Bruxelles)H-Index: 6
Last. Christos Sotiriou (ULB: Université libre de Bruxelles)H-Index: 83
view all 7 authors...
Abstract Background Recent efforts of genome-wide gene expression profiling analyses have improved our understanding of the biological complexity and diversity of triple-negative breast cancers (TNBCs) reporting, at least six different molecular subtypes of TNBC namely Basal-like 1 (BL1), basal-like 2 (BL2), immunomodulatory (IM), mesenchymal (M), mesenchymal stem-like (MSL) and luminal androgen receptor (LAR). However, little is known regarding the potential driving molecular events within each...
81 CitationsSource
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