Sec3 knockdown inhibits TGF-β induced epithelial-mesenchymal transition through the down-regulation of Akt phosphorylation in A549 cells

Xiaohan Qian; Xiaoxu Zhou; Ping Shentu; Yuanfa Yao; Demin Jiao; Qingyong Chen; Jianying Zhou; Yingke Xu

doi:10.1016/j.bbrc.2019.08.145

Sec3 knockdown inhibits TGF-β induced epithelial-mesenchymal transition through the down-regulation of Akt phosphorylation in A549 cells

Biochem Biophys Res Commun. 2019 Nov 5;519(2):253-260. doi: 10.1016/j.bbrc.2019.08.145. Epub 2019 Sep 5.

Authors

Xiaohan Qian¹, Xiaoxu Zhou², Ping Shentu², Yuanfa Yao², Demin Jiao³, Qingyong Chen³, Jianying Zhou⁴, Yingke Xu⁵

Affiliations

¹ Department of Biomedical Engineering, Key Laboratory of Biomedical Engineering of Ministry of Education, Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou, 310027, China; Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
² Department of Biomedical Engineering, Key Laboratory of Biomedical Engineering of Ministry of Education, Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou, 310027, China.
³ Department of Respiratory Oncology, The 903rd Hospital of PLA, Hangzhou, 310013, China.
⁴ Department of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.
⁵ Department of Biomedical Engineering, Key Laboratory of Biomedical Engineering of Ministry of Education, Zhejiang Provincial Key Laboratory of Cardio-Cerebral Vascular Detection Technology and Medicinal Effectiveness Appraisal, Zhejiang University, Hangzhou, 310027, China; Department of Endocrinology, The Affiliated Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, China. Electronic address: yingkexu@zju.edu.cn.

PMID: 31495494
DOI: 10.1016/j.bbrc.2019.08.145

Abstract

The exocyst, an evolutionarily conserved octomeric protein complex, has been demonstrated as an essential component for vesicle tethering during cell exocytosis, and participates in various physiological processes in the cell. Although subunits of the exocyst complex have been reported to be involved in the regulation of TGF-β induced cancer cell migration and epithelial-mesenchymal transition (EMT), the potential function of Sec3 in these regulated processes remains unclear. Here, we show that Sec3 knockdown abolishes TGF-β stimulated A549 lung cancer cell migration in vitro and causes defects in the regulated EMT process. In addition, we find that depletion of Sec3 significantly inhibits TGF-β stimulated Akt phosphorylation in A549 cells, whereas the increase of Smad2 phosphorylation is unaffected. Furthermore, replenishment of an RNAi-resistant form of Sec3 is shown to restore the defects of TGF-β induced cell migration, EMT and Akt signaling activation. In summary, our study provides evidence that Sec3 is involved in TGF-β induced cell migration and EMT processes, presumably through the regulation of PI3K/Akt signaling activation in A549 cancer cells.

Keywords: Akt; Cancer; EMT; Exocyst; Sec3; TGF-β.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

A549 Cells
Cell Movement / drug effects
Down-Regulation / drug effects*
Epithelial-Mesenchymal Transition / drug effects*
Humans
Phosphorylation / drug effects
Proto-Oncogene Proteins c-akt / antagonists & inhibitors*
Proto-Oncogene Proteins c-akt / metabolism
Transforming Growth Factor beta / pharmacology*
Vesicular Transport Proteins / deficiency*
Vesicular Transport Proteins / metabolism
Wound Healing / drug effects

Substances

Exoc1 protein, human
Transforming Growth Factor beta
Vesicular Transport Proteins
Proto-Oncogene Proteins c-akt