C1orf106, an innate immunity activator, is amplified in breast cancer and is required for basal-like/luminal progenitor fate decision
C1orf106, an innate immunity activator, is amplified in breast cancer and is required for basal-like/luminal progenitor fate decision
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C1orf106 是一种先天免疫激活剂，在乳腺癌中被扩增，并且是基底样/腔祖细胞命运决定所必需的
DOI：
10.1007/s11427-019-9570-y
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发表时间：
2019-09-01
影响因子：
9.1
通讯作者：
Zhang, Hongquan
中科院分区：
文献类型：
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作者：
Ma, Ji;Liu, Cheng;Zhang, Hongquan
具有管腔祖细胞基因表达谱的基底样乳腺癌是乳腺癌的侵袭性亚型，与其他亚型相比预后较差。然而，特异性促进基底样乳腺癌发展的基因在很大程度上仍然未知。在此，我们报道了一个新基因C1 orf 106在维持基底样/管腔型前体细胞的特征中起着重要作用。C1 orf 106在基底样乳腺癌中频繁扩增和过表达，并与患者的不良预后相关。在人类TCGA数据库中，C1 orf 106表达与ELF 5的上调和GATA 3的下调相关，这两个转录因子调节乳腺干细胞的命运。C1 orf 106的表达增强促进肿瘤进展和基底样/管腔祖细胞标志物ELF 5的表达; C1 orf 106的缺失抑制肿瘤发生和基底样/管腔祖细胞标志物GATA 3的表达。这些发现表明C1 orf 106通过平衡ELF 5和GATA 3的表达来维持基底样/管腔祖细胞的特征。综上所述，我们证明了C1 orf 106是基底样/管腔祖细胞的重要调节因子，靶向C1 orf 106对乳腺癌具有治疗价值。
Basal-like breast cancer with a luminal progenitor gene expression profile is an aggressive subtype of breast cancer with a poorer prognosis compared with other subtypes. However, genes that specifically promote basal-like breast cancer development remain largely unknown. Here, we report that a novel geneC1orf106plays an important role in maintaining the feature of basal-like/luminal progenitors.C1orf106is frequently amplified and overexpressed in basal-like breast cancer and is associated with a poor outcome in patients. In human TCGA database,C1orf106expression was correlated with upregulation of ELF5 and downregulation of GATA3, two transcription factors that regulate mammary gland stem cell fate. Enhanced expression ofC1orf106promotes tumor progression and expression of basal-like/luminal progenitor marker ELF5; depletion ofC1orf106suppresses tumorigenesis and expression of basal-like/luminal progenitor marker GATA3. These findings suggest thatC1orf106maintains the basal-like/luminal progenitor character through balancing the expression of ELF5 and GATA3. Taken together, we demonstrated thatC1orf106is an important regulator for basal-like/luminal progenitors and targetingC1orf106is of therapeutic value for breast cancer.