Modification of BRCA1-associated breast cancer risk by HMMR overexpression.
Modification of BRCA1-associated breast cancer risk by HMMR overexpression.
复制标题
HMMR 过表达改变 BRCA1 相关乳腺癌风险。
DOI：
10.1038/s41467-022-29335-z
复制
发表时间：
2022-04-07
影响因子：
16.6
通讯作者：
Pujana MA
中科院分区：
文献类型：
--
作者：
Mateo F;He Z;Mei L;de Garibay GR;Herranz C;García N;Lorentzian A;Baiges A;Blommaert E;Gómez A;Mirallas O;Garrido-Utrilla A;Palomero L;Espín R;Extremera AI;Soler-Monsó MT;Petit A;Li R;Brunet J;Chen K;Tan S;Eaves CJ;McCloskey C;Hakem R;Khokha R;Lange PF;Lázaro C;Maxwell CA;Pujana MA
Breast cancer risk for carriers of BRCA1 pathological variants is modified by genetic factors. Genetic variation in HMMR may contribute to this effect. However, the impact of risk modifiers on cancer biology remains undetermined and the biological basis of increased risk is poorly understood. Here, we depict an interplay of molecular, cellular, and tissue microenvironment alterations that increase BRCA1-associated breast cancer risk. Analysis of genome-wide association results suggests that diverse biological processes, including links to BRCA1-HMMR profiles, influence risk. HMMR overexpression in mouse mammary epithelium increases Brca1-mutant tumorigenesis by modulating the cancer cell phenotype and tumor microenvironment. Elevated HMMR activates AURKA and reduces ARPC2 localization in the mitotic cell cortex, which is correlated with micronucleation and activation of cGAS-STING and non-canonical NF-κB signaling. The initial tumorigenic events are genomic instability, epithelial-to-mesenchymal transition, and tissue infiltration of tumor-associated macrophages. The findings reveal a biological foundation for increased risk of BRCA1-associated breast cancer. The effect of hyaluronan-mediated motility receptor (HMMR) expression in BRCA1-associated breast cancer risk remains unknown. Here, HMMR overexpression induces the activation of cGAS-STING and non-canonical NF-κB signalling, instigating an immune permissive environment for breast cancer development.
登录
查看更多内容
影响因子：
16.6
作者：
Bach K;Pensa S;Zarocsinceva M;Kania K;Stockis J;Pinaud S;Lazarus KA;Shehata M;Simões BM;Greenhalgh AR;Howell SJ;Clarke RB;Caldas C;Halim TYF;Marioni JC;Khaled WT
通讯作者：
Khaled WT
染色体不稳定性通过胞质DNA反应驱动转移。
影响因子：
64.8
作者：
Bakhoum SF;Ngo B;Laughney AM;Cavallo JA;Murphy CJ;Ly P;Shah P;Sriram RK;Watkins TBK;Taunk NK;Duran M;Pauli C;Shaw C;Chadalavada K;Rajasekhar VK;Genovese G;Venkatesan S;Birkbak NJ;McGranahan N;Lundquist M;LaPlant Q;Healey JH;Elemento O;Chung CH;Lee NY;Imielenski M;Nanjangud G;Pe'er D;Cleveland DW;Powell SN;Lammerding J;Swanton C;Cantley LC
通讯作者：
Cantley LC
ATM 和 IFI16 对 DNA 传感适配器 STING 的非规范激活可在核 DNA 损伤后介导 NF-κB 信号转导。
影响因子：
16
作者：
Dunphy G;Flannery SM;Almine JF;Connolly DJ;Paulus C;Jønsson KL;Jakobsen MR;Nevels MM;Bowie AG;Unterholzner L
通讯作者：
Unterholzner L
DOI：
10.1038/s41577-021-00524-z
发表时间：
2021-09
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Decout A;Katz JD;Venkatraman S;Ablasser A
通讯作者：
Ablasser A
影响因子：
4.3
作者：
Chen, Helen;Mohan, Pooja;Maxwell, Christopher A.
通讯作者：
Maxwell, Christopher A.