分子细胞生物学报（英文版）

Rui Liu12; Jinzeng Wang14; Masao Ukai11; Ki Sewon15; Pei Chen13; Yutaka Suzuki16; Haiyun Wang; Kazuyuki Aihara; Mariko Okada-Hatakeyama; Luonan Chen

2019

:10.1093/jmcb/mjy059

Journal of Molecular Cell Biology   影响因子和分区

1674-2788

Acquired drug resistance is the major reason why patients fail to respond to cancer therapies.It is a challenging task to determine the tipping point of endocrine resistance and detect the associated molecules.Derived from new systems biology theory,the dynamic network biomarker (DNB) method is designed to quantitatively identify the tipping point of a drastic system transition and can theoretically identify DNB genes that play key roles in acquiring drug resistance.We analyzed time-course mRNA sequence data generated from the tamoxifen-treated estrogen receptor (ER)-positive MCF-7 cell line,and identified the tipping point of endocrine resistance with its leading molecules.The results show that there is interplay between gene mutations and DNB genes,in which the accumulated mutations eventually affect the DNB genes that subsequently cause the change of transcriptional landscape,enabling full-blown drug resistance.Survival analyses based on clinical datasets validated that the DNB genes were associated with the poor survival of breast cancer patients.The results provided the detection for the pre-resistance state or early signs of endocrine resistance.Our predictive method may greatly benefit the scheduling of treatments for complex diseases in which patients are exposed to considerably different drugs and may become drug resistant.

drug resistance breast cancer tipping point dynamic network biomarker (DNB) molecular network mRNA-seq

英语

其他

(This work was supported by grants from the National Key R&D Program of China )%(Strategic Priority Research Program of the Chinese Academy of Sciences )%(the National Natural Science Foundation of China )%(Pearl River Science and Technology Nova Program of Guangzhou )%FISRT,Aihara Innovative Mathematical Modeling Project from Cabinet Office,Japan%(Fundamental Research Funds for the Central Universities )%(JSPS KAKENHI )%Grant-in-Aid for Scientific Research on Innovative Areas (3901) and SPS KAKENHI (15KT0084.17H06299.17H06302.and 18H04031)%(RIKEN Epigenome and Single Cell Project Grants to M.O.-H.This work was performed in part under the International Cooperative Research Program of Institute for Protein Research,Osaka University )

MOLECULAR BIOLOGY & GENETICS

WanFang

perioarticalsyswxb201908004

1.School of Mathematics, South China University of Science and Technology, Guangzhou 510640, China
2.School of Life Sciences and Technology, Tongji University, Shanghai 200092, China;National Research Center for Translational Medicine (Shanghai), Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
3.Graduate School of Medical Life Science, Yokohama City University, Yokohama 230-0045, Japan;Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama 230-0045, Japan
4.Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama 230-0045, Japan
5.School of Mathematics, South China University of Science and Technology, Guangzhou 510640, China;Key Laboratory of Systems Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China
6.Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8562, Japan
7.School of Life Sciences and Technology, Tongji University, Shanghai 200092, China
8.Institute of Industrial Science, The University of Tokyo, Tokyo 153-8505, Japan
9.Graduate School of Medical Life Science, Yokohama City University, Yokohama 230-0045, Japan;Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS), Yokohama 230-0045, Japan;Laboratory of Cell Systems, Osaka University, Osaka 565-0871, Japan
10.Key Laboratory of Systems Biology, Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China;Institute of Industrial Science, The University of Tokyo, Tokyo 153-8505, Japan;Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China;School of Life Science a
11.南方科技大学
12.同济大学
13.横滨城市大学
14.日本横滨市RIKEN综合医学中心
15.东京大学
16.中国科学院生物化学与细胞生物学研究所

Rui Liu,Jinzeng Wang,Masao Ukai,等. 分子细胞生物学报（英文版）[J]. Journal of Molecular Cell Biology,2019,11(8):649-664.

Rui Liu.,Jinzeng Wang.,Masao Ukai.,Ki Sewon.,Pei Chen.,...&Luonan Chen.(2019).分子细胞生物学报（英文版）.Journal of Molecular Cell Biology,11(8),649-664.

Rui Liu,et al."分子细胞生物学报（英文版）".Journal of Molecular Cell Biology 11.8(2019):649-664.