Identification of a novel ER-NFĸB-driven stem-like cell population associated with relapse of ER+ breast tumors.
Identification of a novel ER-NFĸB-driven stem-like cell population associated with relapse of ER+ breast tumors.
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DOI：
10.1186/s13058-022-01585-1
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发表时间：
2022-12-08
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影响因子：
--
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中科院分区：
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--
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高达 40% 的雌激素受体阳性 (ER+) 乳腺癌患者会出现复发。这可以归因于乳腺癌干细胞（BCSC），已知它们与治疗耐药、复发和转移有关。因此，迫切需要确定在 ER+ 乳腺肿瘤中驱动干细胞样细胞特性的基因/途径。利用单细胞 RNA 测序和各种生物信息学方法，我们鉴定了一个独特的干细胞样群体并建立了其临床相关性。通过后续研究，我们验证了我们的生物信息学研究结果，并证实了 ER 和 NFĸB 在促进乳腺癌细胞系和患者衍生模型中干细胞样特性中的作用。我们在多个 ER+ 乳腺癌模型中发现了一种由 ER 和 NFĸB 驱动的新型静止干细胞样细胞群。此外，我们发现源自这种干细胞样群体的基因特征在原发性 ER+ 乳腺肿瘤、内分泌治疗耐药和转移细胞群体中表达，并预示着患者预后不良。这些发现表明 ER 和 NFĸB 串扰在 BCSC 生物学中的新作用，并且了解这些途径促进干特性的机制可用于改善有复发风险的 ER+ 乳腺癌患者的预后。在线版本包含可在 10.1186/s13058-022-01585-1 获取的补充材料。
Up to 40% of patients with estrogen receptor-positive (ER+) breast cancer experience relapse. This can be attributed to breast cancer stem cells (BCSCs), which are known to be involved in therapy resistance, relapse, and metastasis. Therefore, there is an urgent need to identify genes/pathways that drive stem-like cell properties in ER+ breast tumors. Using single-cell RNA sequencing and various bioinformatics approaches, we identified a unique stem-like population and established its clinical relevance. With follow-up studies, we validated our bioinformatics findings and confirmed the role of ER and NFĸB in the promotion of stem-like properties in breast cancer cell lines and patient-derived models. We identified a novel quiescent stem-like cell population that is driven by ER and NFĸB in multiple ER+ breast cancer models. Moreover, we found that a gene signature derived from this stem-like population is expressed in primary ER+ breast tumors, endocrine therapy-resistant and metastatic cell populations and predictive of poor patient outcome. These findings indicate a novel role for ER and NFĸB crosstalk in BCSCs biology and understanding the mechanism by which these pathways promote stem properties can be exploited to improve outcomes for ER+ breast cancer patients at risk of relapse. The online version contains supplementary material available at 10.1186/s13058-022-01585-1.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
7.4
作者：
Fillmore, Christine M.;Kuperwasser, Charlotte
通讯作者：
Kuperwasser, Charlotte
DOI：
10.1186/bcr2106
发表时间：
2008
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Grimshaw MJ;Cooper L;Papazisis K;Coleman JA;Bohnenkamp HR;Chiapero-Stanke L;Taylor-Papadimitriou J;Burchell JM
通讯作者：
Burchell JM
影响因子：
11.2
作者：
Harrison, Hannah;Rogerson, Lynsey;Landberg, Goran
通讯作者：
Landberg, Goran