Rac1 activates non-oxidative pentose phosphate pathway to induce chemoresistance of breast cancer

Li, Qingjian; Qin, Tao; Bi, Zhuofei; Hong, Huangming; Ding, Lin; Chen, Jiewen; Wu, Wei; Lin, Xiaorong; Fu, Wenkui; Zheng, Fang; Yao, Yihong; Luo, Man‐Li; Saw, Phei Er; Wulf, Gerburg M.; Xu, Xiaoding; Song, Erwei; Yao, Herui; Hu, Hai

doi:10.1038/s41467-020-15308-7

Cited by 124 publications

(80 citation statements)

References 60 publications

(85 reference statements)

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“…related to the progress of human breast cancer [26][27][28][29][30][31]. These data clearly provide useful information for the resistance development of breast cancer.…”

Section: Plos Onementioning

confidence: 73%

Genome-wide DNA methylation analysis of breast cancer MCF-7 / Taxol cells with MeDIP-Seq

Shi

Gong

et al. 2020

PLoS ONE

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Breast cancer (BC) is the most frequently diagnosed tumor in women worldwide. Although the combination of surgery and Taxol chemotherapy can achieve a certain therapeutic effect, patients often develop drug-resistance, resulting in a poor prognosis. Therefore, it is significative to seek the molecular mechanism of chemotherapy resistance. Recent studies have found that abnormal epigenetic regulation in breast cells changes the expression of key genes, which can lead to the occurrence, development, and maintenance of cancer, even related to the development of drug-resistance. Therefore, in this study, we performed methylated DNA immunoprecipitation-sequencing (MeDIP-seq) to reveal the difference in methylation between breast cancer drug-resistant cells and sensitive cells. A total of 55076 differentially methylated genes (DMGs) were detected, including 21061 hypermethylated DMGs and 34015 hypomethylated DMGs. Moreover, Gene Ontology (GO) analysis and KEGG pathway analysis reveal the function and pathway of screening genes. These results indicate that DNA methylation may be involved in regulating the occurrence and development of breast cancer.

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“…related to the progress of human breast cancer [26][27][28][29][30][31]. These data clearly provide useful information for the resistance development of breast cancer.…”

Section: Plos Onementioning

confidence: 73%

Genome-wide DNA methylation analysis of breast cancer MCF-7 / Taxol cells with MeDIP-Seq

Shi

Gong

et al. 2020

PLoS ONE

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“…It has now become increasingly evident that benefits of glycolysis extend beyond metabolism and role of altered glycolysis has been implicated in transcriptional regulation (10), epigenetic regulation (11,12), immune-escape (13), cell cycle (14), mitotic spindle (15), metastasis (16), and inflammation (17). Moreover, aerobic glycolysis and associated pathways contribute to chemoand radio-resistance in cancer (18)(19)(20). Combinatorial treatments with compounds inhibiting glycolysis have shown synergy in decreasing triple-negative breast cancer cell viability (21).…”

Section: Introductionmentioning

confidence: 99%

Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer

Iqbal

Siddiqui

Rehman

et al. 2020

Preprint

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Striking similarity exists between metabolic changes associated with embryogenesis and tumorigenesis. Chromobox proteins-CBX2/4/6/7/8, core components of canonical polycomb repressor complex 1 (cPRC1), play essential roles in embryonic development and aberrantly expressed in breast cancer. Understanding how altered CBX expression relates to metabolic reprogramming in breast cancer may reveal vulnerabilities of therapeutic pertinence. Using transcriptomic and metabolomic data from breast cancer patients (N>3000 combined), we identified outstanding roles of CBX2 and CBX7 in positive and negative regulation of glucose metabolism, respectively. Genetic ablation experiments validated the contrasting roles of two isoforms in cancer metabolism and cell growth. Furthermore, we determined that contrary effects of CBX2 and CBX7 on breast cancer metabolism were due to differential modulation of the mTORC1 signaling by two isoforms. Underpinning the biological significance of metabolic roles, CBX2 and CBX7 were found to be the most up- and down-regulated isoforms, respectively, in breast tumors compared to normal tissues. Moreover, CBX2 and CBX7 expression (not other isoforms) correlated strongly, but oppositely, with breast tumor aggressiveness. Genomic data showed higher amplification frequency of CBX2, not CBX7, in breast tumors. Highlighting the clinical significance of findings, survival and drug sensitivity analysis revealed that CBX2 and CBX7 predicted patient outcome and sensitivity to clinical drugs. In summary, this work identifies previously unknown antagonistic roles of CBX2 and CBX7 in breast tumor metabolism, and the results presented may have implications in strategies targeting breast cancer metabolism.Significance statementMetabolic reprogramming is a hallmark of cancer. Understanding how reprogramming of metabolism is regulated in cancer may reveal therapeutically relevant targets. Using integrative approach, we elucidate the hitherto unknown antagonistic roles of CBX2 and CBX7 in breast cancer metabolism. Highlighting the relevance of identified metabolic roles, we found that CBX2 and CBX7 (not other members) are the most differentially expressed isoforms in breast tumors (compared to normals) and the only isoforms which significantly correlate with breast cancer aggressiveness. Further, CBX2/7 predicted patient outcome and response to drugs used in breast cancer treatment, underscoring clinical significance of our study. In brief, this work unravels novel metabolic roles of CBX2/7 which may have implications in breast cancer treatment.

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“…Another study found that ERK activation via a member of small G proteins Rac1 increases nucleotide metabolism in breast cancer cells and protects against chemotherapy-induced cytotoxicity and DNA damage. Rac1 is also upregulated in chemoresistant breast cancer and correlates with poor prognosis [ 139 ].…”

Section: The Cxcl12/cxcr4-induced Therapy Resistance In Breast Camentioning

confidence: 99%

The Signaling Duo CXCL12 and CXCR4: Chemokine Fuel for Breast Cancer Tumorigenesis

Zielińska

Katanaev

2020

Cancers

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The CXCL12/CXCR4 signaling pathway has emerged in the recent years as a key player in breast cancer tumorigenesis. This pathway controls many aspects of breast cancer development including cancer cell proliferation, motility and metastasis to all target organs. Moreover, the CXCL12/CXCR4 cascade affects both immune and stromal cells, creating tumor-supporting microenvironment. In this review, we examine state-of-the-art knowledge about detrimental roles of the CXCL12/CXCR4 signaling, discuss its therapeutic potential and suggest further research directions beneficial both for basic research and personalized medicine in breast cancer.

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Rac1 activates non-oxidative pentose phosphate pathway to induce chemoresistance of breast cancer

Cited by 124 publications

References 60 publications

Genome-wide DNA methylation analysis of breast cancer MCF-7 / Taxol cells with MeDIP-Seq

Genome-wide DNA methylation analysis of breast cancer MCF-7 / Taxol cells with MeDIP-Seq

Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer

The Signaling Duo CXCL12 and CXCR4: Chemokine Fuel for Breast Cancer Tumorigenesis

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