TUSC3 induces autophagy in human non-small cell lung cancer cells through Wnt/β-catenin signaling.
Identifieur interne : 000C94 ( Main/Exploration ); précédent : 000C93; suivant : 000C95TUSC3 induces autophagy in human non-small cell lung cancer cells through Wnt/β-catenin signaling.
Auteurs : Yun Peng [République populaire de Chine] ; Jun Cao [République populaire de Chine] ; Xiao-Yi Yao [République populaire de Chine] ; Jian-Xin Wang [République populaire de Chine] ; Mei-Zuo Zhong [République populaire de Chine] ; Ping-Ping Gan [République populaire de Chine] ; Jian-Huang Li [République populaire de Chine]Source :
- Oncotarget [ 1949-2553 ] ; 2017.
Abstract
We investigated the effects of tumor suppressor candidate 3 (TUSC3) on autophagy in human non-small cell lung cancer (NSCLC) cells. A total of 118 NSCLC patients (88 males and 30 females) who underwent surgery at our institute were enrolled in the study. Immunohistochemical analysis revealed that TUSC3 protein expression was lower in NSCLC specimens than adjacent normal tissue. Correspondingly, there was greater methylation of TUSC3 in NSCLC than adjacent normal tissue. After transient transfection of A549 NSCLC cells with constructs designed to up-regulate or down-regulate TUSC3 expression, we analyzed the effects of inhibiting the Wnt pathway (XAV939) and autophagy (chloroquine, CQ) on the behavior of NSCLC cells. We also performed TOP/FOP-Flash reporter assays, MTT assays, Annexin V-FITC/propidium iodide staining, and acridine orange staining to evaluate Wnt/β-catenin signaling, cell proliferation, apoptosis, and autophagy, respectively. Expression of Wnt/β-catenin pathway components and autophagy-related proteins was analyzed using qRT-PCR and Western blotting. We found that TUSC3 inhibited cell proliferation and promoted both apoptosis and autophagy in A549 cells. In addition, TUSC3 increased expression of autophagy-related proteins. It also increased expression of Wnt/β-catenin signaling pathway components and promoted nuclear transfer of β-catenin, resulting in activation of Wnt/β-catenin signaling. TUSC3 thus induces autophagy in human NSCLC cells through activation of the Wnt/β-catenin signaling pathway.
DOI: 10.18632/oncotarget.17674
PubMed: 28881786
Affiliations:
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<front><div type="abstract" xml:lang="en">We investigated the effects of tumor suppressor candidate 3 (<i>TUSC3</i>
) on autophagy in human non-small cell lung cancer (NSCLC) cells. A total of 118 NSCLC patients (88 males and 30 females) who underwent surgery at our institute were enrolled in the study. Immunohistochemical analysis revealed that TUSC3 protein expression was lower in NSCLC specimens than adjacent normal tissue. Correspondingly, there was greater methylation of <i>TUSC3</i>
in NSCLC than adjacent normal tissue. After transient transfection of A549 NSCLC cells with constructs designed to up-regulate or down-regulate TUSC3 expression, we analyzed the effects of inhibiting the Wnt pathway (XAV939) and autophagy (chloroquine, CQ) on the behavior of NSCLC cells. We also performed TOP/FOP-Flash reporter assays, MTT assays, Annexin V-FITC/propidium iodide staining, and acridine orange staining to evaluate Wnt/β-catenin signaling, cell proliferation, apoptosis, and autophagy, respectively. Expression of Wnt/β-catenin pathway components and autophagy-related proteins was analyzed using qRT-PCR and Western blotting. We found that TUSC3 inhibited cell proliferation and promoted both apoptosis and autophagy in A549 cells. In addition, TUSC3 increased expression of autophagy-related proteins. It also increased expression of Wnt/β-catenin signaling pathway components and promoted nuclear transfer of β-catenin, resulting in activation of Wnt/β-catenin signaling. TUSC3 thus induces autophagy in human NSCLC cells through activation of the Wnt/β-catenin signaling pathway.</div>
</front>
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<name sortKey="Cao, Jun" sort="Cao, Jun" uniqKey="Cao J" first="Jun" last="Cao">Jun Cao</name>
<name sortKey="Gan, Ping Ping" sort="Gan, Ping Ping" uniqKey="Gan P" first="Ping-Ping" last="Gan">Ping-Ping Gan</name>
<name sortKey="Li, Jian Huang" sort="Li, Jian Huang" uniqKey="Li J" first="Jian-Huang" last="Li">Jian-Huang Li</name>
<name sortKey="Wang, Jian Xin" sort="Wang, Jian Xin" uniqKey="Wang J" first="Jian-Xin" last="Wang">Jian-Xin Wang</name>
<name sortKey="Yao, Xiao Yi" sort="Yao, Xiao Yi" uniqKey="Yao X" first="Xiao-Yi" last="Yao">Xiao-Yi Yao</name>
<name sortKey="Zhong, Mei Zuo" sort="Zhong, Mei Zuo" uniqKey="Zhong M" first="Mei-Zuo" last="Zhong">Mei-Zuo Zhong</name>
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