Dishevelled family proteins are expressed in non-small cell lung cancer and function differentially on tumor progression

Wei, Qiang; Zhao, Yue; Yang, Zujing; Dong, Qianze; Dong, Xin-Jun; Han, Yang; Zhao, Chen; Wang, Enhua

doi:10.1016/j.lungcan.2008.06.018

Cited by 62 publications

(60 citation statements)

References 42 publications

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“…Previously, we found that nodal metastases had higher levels of Dvl-1 and Dvl-3 expression than primary tumors, and that Dvl-1 expression correlated with b-catenin expression in metastases. Exogenous expression of Dvl-1 and Dvl-3 in lung cancer cells strikingly increased cell invasiveness, but differentially altered b-catenin protein expression [23]. These results strongly suggest that despite Dvl family members enhancing invasiveness of lung cancer cells, they do so by different mechanisms.…”

Section: Discussionmentioning

confidence: 83%

“…Although there are increasing reports of Dvl overexpression in breast cancer, prostate cancer, cervical cancer, liver cancer, and lung cancer, expression of Dvl family members is very controversial [18][19][20][21][22], and their correlation with tumor prognosis is not clear. We have confirmed that Dvl-1 and Dvl-3 are abnormally expressed in nonsmall cell lung cancer (NSCLC), and affect lung cancer cell invasiveness and metastasis [23]. Herein, we assessed the expression of Dvl-1, Dvl-3, b-catenin, and p120ctn (a member of the catenin family) and analyzed the correlation between their expression and prognosis in NSCLC tissues.…”

Section: Introductionmentioning

confidence: 91%

“…All specimens were evaluated by two investigators who were unaware of the clinical data. When Dvl-1 and Dvl-3 were expressed in more than 10% tumor cells, we considered as positive expression of the proteins [23]. b-Catenin and p120ctn ''normal expression'' were defined when over 90% of the tumor cells showed continuous and clear cell membranous staining.…”

Section: Evaluation Of Immunohistochemistrymentioning

confidence: 99%

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Dishevelled-1 and dishevelled-3 affect cell invasion mainly through canonical and noncanonical Wnt pathway, respectively, and associate with poor prognosis in nonsmall cell lung cancer

et al. 2010

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Dishevelled (Dvl) family proteins are overexpressed in nonsmall cell lung cancer (NSCLC), but the correlation between Dvl overexpression and patient prognosis is not clear. The underlying mechanisms of Dvl-1 and Dvl-3 promoting lung cancer cell invasion require further research. We used immunohistochemistry to assess the presence of Dvl-1, Dvl-3, beta-catenin, and p120ctn, and compared their expression to the prognosis in 102 specimens from NSCLC patients. We also examined the effect of Dvl-1 and Dvl-3 on Tcf-dependent transcriptional activity, as well as on the invasiveness in A549 and LTEP-alpha-2 lung cancer cells. The results showed that Dvl-1 correlated to the abnormal expression of beta-catenin, while Dvl-3 correlated to p120ctn. Both Dvl-1 and Dvl-3 were related to the poor prognosis of patient. Dvl-1 overexpression enhanced the Tcf-dependent transcriptional activity and beta-catenin expression significantly. However, Dvl-3 had little effect on the Tcf-dependent transcriptional activity and beta-catenin expression, which was accompanied by p38 and JNK phosphorylation. Furthermore, the invasiveness of Dvl-3-enhanced cells was inhibited by p38 and JNK inhibitors. Exogenous expression of both Dvl-1 and Dvl-3 increased the p120ctn protein expression, while only Dvl-3 upregulated p120ctn mRNA. We conclude that both protein and mRNA of Dvl-1 and Dvl-3 are overexpressed in NSCLC in a manner related to poor prognosis. Dvl-1 may affect the biological behavior of lung cancer cells mainly through beta-catenin (canonical Wnt pathway), while Dvl-3 mainly through p38 and JNK pathway (noncanonical Wnt pathway).

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 91%

Section: Evaluation Of Immunohistochemistrymentioning

confidence: 99%

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Dishevelled-1 and dishevelled-3 affect cell invasion mainly through canonical and noncanonical Wnt pathway, respectively, and associate with poor prognosis in nonsmall cell lung cancer

et al. 2010

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“…DVLS localize primarily to the cytoplasm and, to a lesser extent, the cell membrane (8)(9)(10)(11). We previously demonstrated overexpression and primarily cytoplasmic localization of all three DVL family proteins (DVL-1, DVL-2, and DVL-3) in non-small cell lung cancer (NSCLC; ref.…”

Section: Introductionmentioning

confidence: 99%

“…We previously demonstrated overexpression and primarily cytoplasmic localization of all three DVL family proteins (DVL-1, DVL-2, and DVL-3) in non-small cell lung cancer (NSCLC; ref. 11). This overexpression of DVLS enhanced P38 and JNK signaling and promoted proliferation and metastasis in NSCLC cells (12).…”

Section: Introductionmentioning

confidence: 99%

Cytosolic TMEM88 Promotes Invasion and Metastasis in Lung Cancer Cells by Binding DVLS

Zhang

Jiang

et al. 2015

Cancer Research

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Transmembrane protein 88 (TMEM88) is a transmembrane protein that plays a crucial role in regulating human stem cell differentiation and embryonic development. However, its expression and clinicopathologic significance in human neoplasms is unclear. In this study, the expression and subcellular localizations of TMEM88 were assessed in 214 cases of non-small cell lung cancer (NSCLC). Notably, TMEM88 was highly expressed in the cytosol of $60% NSCLC specimens examined. Higher expression of cytosolic TMEM88 in NSCLC correlated significantly with poor differentiation, high TNM stage, lymph node metastasis, and inferior survival. In NSCLC cells displaying membrane-localized TMEM88, we observed an inhibition of canonical Wnt signaling due to interactions of TMEM88 with the Wnt pathway factor Dishevelled (DVLS). In contrast, NSCLC cells with cytosol-localized TMEM88 lacked effects on Wnt signaling. Cytosolic interactions of TMEM88 and DVLS increased the expression of phosphorylated, active forms of p38, GSK3b (Thr390), and Snail, thereby reducing the expression of the tight junction-associated proteins ZO-1 and occludin, effects associated with enhanced invasive and metastatic cell characters. Importantly, attenuating the expression of cytosolic TMEM88 reduced metastatic prowess in xenograft models. Overall, our findings show how mislocalization of TMEM88 to the cytosol in NSCLC cells ablates its Wnt pathway regulatory properties, thereby promoting invasion and metastasis by activating the p38-GSK3b-Snail signaling pathway. Cancer Res; 75(21); 4527-37. Ó2015 AACR.

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2012

Hepatology

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Dishevelled family proteins are expressed in non-small cell lung cancer and function differentially on tumor progression

Cited by 62 publications

References 42 publications

Dishevelled-1 and dishevelled-3 affect cell invasion mainly through canonical and noncanonical Wnt pathway, respectively, and associate with poor prognosis in nonsmall cell lung cancer

Dishevelled-1 and dishevelled-3 affect cell invasion mainly through canonical and noncanonical Wnt pathway, respectively, and associate with poor prognosis in nonsmall cell lung cancer

Cytosolic TMEM88 Promotes Invasion and Metastasis in Lung Cancer Cells by Binding DVLS

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