TY - JOUR
T1 - TSLP enhances progestin response in endometrial cancer via androgen receptor signal pathway
AU - Lv, Mu
AU - Xu, Yuan
AU - Chen, Peiqin
AU - Li, Jingjie
AU - Qin, Zuoshu
AU - Huang, Baozhu
AU - Liu, Yong
AU - Tao, Xiang
AU - Xiang, Jun
AU - Wang, Yanqiu
AU - Feng, Youji
AU - Zheng, Wenxin
AU - Zhang, Zhenbo
AU - Li, Linxia
AU - Liao, Hong
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature Limited 2023.
PY - 2024/3/9
Y1 - 2024/3/9
N2 - Background: The enriched proteins within in vitro fertilisation (IVF)-generated human embryonic microenvironment could reverse progestin resistance in endometrial cancer (EC). Methods: The expression of thymic stromal lymphopoietin (TSLP) in EC was evaluated by immunoblot and IHC analysis. Transcriptome sequencing screened out the downstream pathway regulated by TSLP. The role of TSLP, androgen receptor (AR) and KANK1 in regulating the sensitivity of EC to progestin was verified through a series of in vitro and in vivo experiments. Results: TSLP facilitates the formation of a BMP4/BMP7 heterodimer, resulting in activation of Smad5, augmenting AR signalling. AR in turn sensitises EC cells to progestin via KANK1. Downregulation of TSLP, loss of AR and KANK1 in EC patients are associated with tumour malignant progress. Moreover, exogenous TSLP could rescue the anti-tumour effect of progestin on mouse in vivo xenograft tumour. Conclusions: Our findings suggest that TSLP enhances the sensitivity of EC to progestin through the BMP4/Smad5/AR/KANK1 axis, and provide a link between embryo development and cancer progress, paving the way for the establishment of novel strategy overcoming progestin resistance using embryo original factors. (Figure presented.).
AB - Background: The enriched proteins within in vitro fertilisation (IVF)-generated human embryonic microenvironment could reverse progestin resistance in endometrial cancer (EC). Methods: The expression of thymic stromal lymphopoietin (TSLP) in EC was evaluated by immunoblot and IHC analysis. Transcriptome sequencing screened out the downstream pathway regulated by TSLP. The role of TSLP, androgen receptor (AR) and KANK1 in regulating the sensitivity of EC to progestin was verified through a series of in vitro and in vivo experiments. Results: TSLP facilitates the formation of a BMP4/BMP7 heterodimer, resulting in activation of Smad5, augmenting AR signalling. AR in turn sensitises EC cells to progestin via KANK1. Downregulation of TSLP, loss of AR and KANK1 in EC patients are associated with tumour malignant progress. Moreover, exogenous TSLP could rescue the anti-tumour effect of progestin on mouse in vivo xenograft tumour. Conclusions: Our findings suggest that TSLP enhances the sensitivity of EC to progestin through the BMP4/Smad5/AR/KANK1 axis, and provide a link between embryo development and cancer progress, paving the way for the establishment of novel strategy overcoming progestin resistance using embryo original factors. (Figure presented.).
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U2 - 10.1038/s41416-023-02545-y
DO - 10.1038/s41416-023-02545-y
M3 - Article
C2 - 38172534
AN - SCOPUS:85181229618
SN - 0007-0920
VL - 130
SP - 585
EP - 596
JO - British journal of cancer
JF - British journal of cancer
IS - 4
ER -