Therapeutic protein PAK restrains the progression of triple negative breast cancer through degrading SREBP-1 mRNA

作者全名："Hu, Pan; Zhou, Peiyi; Sun, Tieyun; Liu, Dingkang; Yin, Jun; Liu, Lubin"

作者地址："[Hu, Pan; Zhou, Peiyi; Sun, Tieyun; Liu, Lubin] Chongqing Med Univ, Women & Childrens Hosp, Dept Obstet & Gynecol, 120 Longshan Rd, Chongqing 401147, Peoples R China; [Liu, Dingkang; Yin, Jun] China Pharmaceut Univ, Sch Life Sci & Technol, Jiangsu Key Lab Druggabil Biopharmaceut, Nanjing 210009, Peoples R China; [Liu, Dingkang; Yin, Jun] China Pharmaceut Univ, Sch Life Sci & Technol, State Key Lab Nat Med, Nanjing 210009, Peoples R China"

通信作者："Liu, LB (通讯作者)，Chongqing Med Univ, Women & Childrens Hosp, Dept Obstet & Gynecol, 120 Longshan Rd, Chongqing 401147, Peoples R China.; Yin, J (通讯作者)，China Pharmaceut Univ, Sch Life Sci & Technol, Jiangsu Key Lab Druggabil Biopharmaceut, Nanjing 210009, Peoples R China.; Yin, J (通讯作者)，China Pharmaceut Univ, Sch Life Sci & Technol, State Key Lab Nat Med, Nanjing 210009, Peoples R China."

来源：BREAST CANCER RESEARCH

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001123717500001

JCR分区：Q1

影响因子：7.4

年份：2023

卷号：25

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Therapeutic protein; Lipogenesis; Fatty acid; SREBP-1; Triple negative breast cancer

摘要："Triple-negative breast cancer (TNBC) represents the most challenging subtype of breast cancer. Studies have implicated an upregulation of lipid synthesis pathways in the initiation and progression of TNBC. Targeting lipid synthesis pathways may be a promising therapeutic strategy for TNBC. Our previous study developed a therapeutic protein PAK with passive targeting and inhibiting tumor proliferation. In this study, we further substantiate the efficacy of PAK in TNBC. Transcriptome sequencing analysis revealed PAK-mediated downregulation of genes involved in fatty acid synthesis, including key genes like SREBP-1, FASN, and SCD1. RNA immunoprecipitation experiments demonstrated a significant binding affinity of PAK to SREBP-1 mRNA, facilitating its degradation process. Both in vitro and in vivo models, PAK hampered TNBC progression by downregulating lipid synthesis pathways. In conclusion, this study emphasizes that PAK inhibits the progression of TNBC by binding to and degrading SREBP-1 mRNA, revealing a new strategy for regulating lipid synthesis in the intervention of TNBC and its therapeutic significance."

基金机构：National Natural Science Foundation of China

基金资助正文：No Statement Available