Activating transcription factor 6 promotes proliferation, migration and invasion of PC3 human prostate cancer cells through Hippo-YAP signaling pathway

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Activating transcription factor 6 promotes proliferation, migration and invasion of PC3 human prostate cancer cells through Hippo-YAP signaling pathway

Basic Medicine | 更新时间：2026-01-09

- Activating transcription factor 6 promotes proliferation, migration and invasion of PC3 human prostate cancer cells through Hippo-YAP signaling pathway
- Journal of Army Medical University Vol. 45, Issue 1, Pages: 29-37(2023)
- 作者机构：
  
  1.400016 重庆，重庆医科大学附属第一医院泌尿外科
  2.408399 重庆，重庆市垫江县人民医院泌尿外科
- 作者简介：
- 基金信息：
  
  the Program of Natual Science Foundation of Chongqing(cstc2019jcyj-msxmX0732);the Special Project of Science and Technology Innovation of Social Undertakings and People's Livelihood Security of Chongqing(cstc2017shms-zdyf0319)
- DOI：10.16016/j.2097-0927.202208013
  CLC： R394.3;R73-37;R737.25
- Received：02 August 2022，
  
  Revised：2022-09-09，
  
  Published：15 January 2023
- 稿件说明：
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Hengchuan LIU, Zongke YANG, Qingyuan LIU, et al. Activating transcription factor 6 promotes proliferation, migration and invasion of PC3 human prostate cancer cells through Hippo-YAP signaling pathway[J]. Journal of Army Medical University, 2023, 45(1): 29-37.
DOI：

Hengchuan LIU, Zongke YANG, Qingyuan LIU, et al. Activating transcription factor 6 promotes proliferation, migration and invasion of PC3 human prostate cancer cells through Hippo-YAP signaling pathway[J]. Journal of Army Medical University, 2023, 45(1): 29-37. DOI： 10.16016/j.2097-0927.202208013.

摘要

目的

2

探讨转录活化因子6 (activating transcription factor 6

ATF6)对前列腺癌PC3细胞增殖、迁移和侵袭的影响。

方法

2

收集前列腺癌组织标本和前列腺增生组织标本，实时荧光定量PCR(qRT-PCR)和Western blot分别检测ATF6的mRNA和蛋白质水平。通过shRNA慢病毒干扰载体感染PC3细胞，敲降ATF6表达水平。CCK8和EdU实验检测PC3细胞增殖能力，划痕实验和Transwell侵袭实验检测PC3细胞迁移和侵袭能力。采用裸鼠异种移植模型评估ATF6在体内对肿瘤增殖的影响。使用JASPAR数据库预测和荧光素酶报告基因评估Yes相关蛋白(YAP)和ATF6之间的关联。qRT-PCR、免疫荧光检测YAP的mRNA和蛋白质水平。qRT-PCR检测YAP的两个下游因子结缔组织生长因子(CTGF)和富含半胱氨酸的61(Cyr61)的mRNA表达水平。

结果

2

在前列腺癌组织中，ATF6的mRNA和蛋白质水平均显著升高(

P

<

0.05)。敲降ATF6后，PC3细胞的增殖能力、侵袭能力和迁移能力均受到抑制(

P

<

0.05)。动物实验证实敲降ATF6能明显抑制肿瘤生长(

P

<

0.05)。JASPAR数据库预测发现ATF6与YAP之前存在启动结合位点，荧光素酶报告基因证实ATF6与YAP存在相互作用。敲降ATF6后显著下调YAP的mRNA及蛋白质表达水平(

P

<

0.05)，且YAP下游基因CTGF和Cyr61的mRNA表达水平也随之下调(

P

<

0.05)。

结论

2

ATF6能通过Hippo-YAP信号通路促进前列腺癌PC3细胞的增殖、迁移和侵袭。

Abstract

Objective

2

To investigate the effects of activating transcription factor 6 (ATF6) on the proliferation

migration and invasion of prostate cancer PC3 cells.

Methods

2

Prostate cancer tissue samples and benign prostatic hyperplasia tissue samples were collected

then the mRNA and protein levels of ATF6 were detected by qRT-PCR and Western blotting

respectively. Lentivirus with ATF6 shRNA was transfected into PC3 cells to downregulate ATF6 expression

then CCK8 and EdU assays were adopted to determine the proliferation of PC3 cells

and wound-healing and Transwell invasion tests were performed to evaluate the migration and invasion abilities of PC3 cells. Nude mouse xenograft models were used to assess the influence of ATF6 on tumorigenesis

in vivo

. Moreover

the association between Yes-associated protein (YAP) and ATF6 was analyzed using online JASPAR database prediction and luciferase reporter. The mRNA and protein levels of YAP were detected with qRT-PCR and immunofluorescence assay

and the mRNA levels of 2 downstream factors of YAP

connective tissue growth factor (CTGF) and cysteine-rich 61 (Cyr61)

were also measured by qRT-PCR.

Results

2

The mRNA and protein levels of ATF6 in prostate cancer tissues were significantly increased (

P

<

0.05). Knockdown of ATF6 decreased the proliferation

invasion

and migration a

bilities of PC3 cells (

P

<

0.05)

and the

in vivo

study showed that ATF6-knockdown attenuated tumor growth as well (

P

<

0.05). JASPAR database predicted that there was an initiation binding site between ATF6 and YAP

and the luciferase reporter assay also confirmed the interaction between them. In addition

YAP expression was remarkably downregulated after knockdown of ATF6 (

P

<

0.05)

and the mRNA level of YAP downstream genes CTGF and Cyr61 were also decreased accordingly (

P

<

0.05).

Conclusion

2

ATF6 promotes the proliferation

migration

and invasion of prostate cancer PC3 cells through Hippo-YAP signaling pathway.

关键词

Keywords

references

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