TSLP enhances progestin response in endometrial cancer via androgen receptor signal pathway

期刊论文
发表日期：

2024年1月3日

查看全文

Mu Lv,
Yuan Xu,
Peiqin Chen,
Jingjie Li,
Zuoshu Qin,
Baozhu Huang,
Yong Liu,
Xiang Tao,
Jun Xiang,
Yanqiu Wang,
Youji Feng,
Wenxin Zheng,
Zhenbo Zhang,
Linxia Li,
Hong Liao

摘要

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.