Silencing PTEN in the fallopian tube promotes enrichment of cancer stem cell-like function through loss of PAX2.
Silencing PTEN in the fallopian tube promotes enrichment of cancer stem cell-like function through loss of PAX2.
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DOI：
10.1038/s41419-021-03663-2
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发表时间：
2021-04-07
影响因子：
9
通讯作者：
Burdette JE
中科院分区：
文献类型：
--
作者：
Russo A;Colina JA;Moy J;Baligod S;Czarnecki AA;Varughese P;Lantvit DD;Dean MJ;Burdette JE
高级别浆液性卵巢癌（HGSOC）是最致命的妇科恶性肿瘤，主要在转移阶段检测到。大多数HGSOC起源于输卵管上皮（FTE），并在侵入腹膜之前转移到卵巢;因此，使用FTE衍生模型研究疾病的发生和进展至关重要。我们以前证明了FTE中PTEN的丢失会导致卵巢癌。在本研究中，FTE中PTEN的缺失导致癌症干细胞标志物如LGR 5、WNT 4、ALDH 1、CD 44的富集。有趣的是，转录因子PAX 2的丢失，这是HGSOC中常见的早期改变，在癌症干细胞样细胞（CSC）标志物的表达和细胞功能中起着关键作用。此外，PTEN的缺失导致产生具有不同CSC标志物表达、致瘤性和化学抗性谱的两种不同细胞亚群。总之，这些数据表明，由于PAX 2的丢失，PTEN的丢失诱导FTE细胞重编程为更干细胞样表型，并提供了一个模型来研究FTE驱动的卵巢癌肿瘤形成期间的早期事件。
High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy that is primarily detected at the metastatic stage. Most HGSOC originates from the fallopian tube epithelium (FTE) and metastasizes to the ovary before invading the peritoneum; therefore, it is crucial to study disease initiation and progression using FTE-derived models. We previously demonstrated that loss of PTEN from the FTE leads to ovarian cancer. In the present study, loss of PTEN in FTE led to the enrichment of cancer stem cell markers such as LGR5, WNT4, ALDH1, CD44. Interestingly, loss of the transcription factor PAX2, which is a common and early alteration in HGSOC, played a pivotal role in the expression of cancer stem-like cells (CSC) markers and cell function. In addition, loss of PTEN led to the generation of two distinct subpopulations of cells with different CSC marker expression, tumorigenicity, and chemoresistance profiles. Taken together, these data suggest that loss of PTEN induces reprogramming of the FTE cells into a more stem-like phenotype due to loss of PAX2 and provides a model to study early events during the FTE-driven ovarian cancer tumor formation.
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影响因子：
3.9
作者：
King SM;Hilliard TS;Wu LY;Jaffe RC;Fazleabas AT;Burdette JE
通讯作者：
Burdette JE
影响因子：
28.2
作者：
Hanrahan AJ;Schultz N;Westfal ML;Sakr RA;Giri DD;Scarperi S;Janakiraman M;Olvera N;Stevens EV;She QB;Aghajanian C;King TA;Stanchina Ed;Spriggs DR;Heguy A;Taylor BS;Sander C;Rosen N;Levine DA;Solit DB
通讯作者：
Solit DB
影响因子：
--
作者：
Cheaib B;Auguste A;Leary A
通讯作者：
Leary A
影响因子：
2.7
作者：
Gao, XS;Neufeld, TP;Pan, DJ
通讯作者：
Pan, DJ
影响因子：
3.8
作者：
Bernardini, Marcus Q.;Baba, Tsukasa;Berchuck, Andrew
通讯作者：
Berchuck, Andrew