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Supplementary Tables S1-S7 from Cytosolic TMEM88 Promotes Invasion and Metastasis in Lung Cancer Cells by Binding DVLS

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posted on 2023-03-30, 23:04 authored by Xiupeng Zhang, Xinmiao Yu, Guiyang Jiang, Yuan Miao, Liang Wang, Yong Zhang, Yang Liu, Chuifeng Fan, Xuyong Lin, Qianze Dong, Qiang Han, Huanyu Zhao, Yong Han, Xu Han, Xuezhu Rong, Shuting Ding, Endi Wang, Enhua Wang
<p>Supplementary Tables S1-S7: Supplementary TableS1: Clinicopathological features of 40 paired fresh non-small cell lung cancer (NSCLC) samples Supplementary TableS2: Target sequences for siRNA and shRNA Supplementary TableS3: Primers for real-time RT-PCR Supplementary TableS4: Correlation of TMEM88 overexpression and clinicopathological features in 214 cases of non-small cell lung cancer (NSCLC) Supplementary TableS5: Summary of Cox univariate and multivariate regression analysis of the association between clinicopathological features and overall survival in 61 cases of non-small cell lung cancer (NSCLC) Supplementary TableS6: Expression of TMEM88 in various epithelial malignancies Supplementary TableS7: Correlation of cytosolic TMEM88 with the expression of p-P38 and Snail in 50 NSCLC specimens</p>

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ARTICLE ABSTRACT

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, GSK3β (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–GSK3β–Snail signaling pathway. Cancer Res; 75(21); 4527–37. ©2015 AACR.

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    Lung CancerProgression, Invasion & MetastasisMetastasis

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