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EFHD2 promotes epithelial-to-mesenchymal transition and correlates with postsurgical recurrence of stage I lung adenocarcinoma.

EFHD2 promotes epithelial-to-mesenchymal transition and correlates with postsurgical recurrence of stage I lung adenocarcinoma.
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Fan CC, Cheng WC, Huang YC, Sher YP, Liou NJ, Chien YC, Lin PS, Lin PS, Chen CH, Chang WC,


Fan CC, Cheng WC, Huang YC, Sher YP, Liou NJ, Chien YC, Lin PS, Lin PS, Chen CH, Chang WC, (click to view)

Fan CC, Cheng WC, Huang YC, Sher YP, Liou NJ, Chien YC, Lin PS, Lin PS, Chen CH, Chang WC,

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Scientific reports 2017 11 067(1) 14617 doi 10.1038/s41598-017-15186-y
Abstract

Surgery is the only curative treatment for early-stage non-small cell lung cancer (NSCLC) patients. However, approximately one-third of these patients develop recurrence, which remains the main cause of mortality in the postsurgical treatment of NSCLC. Many molecular markers have been proposed to predict recurrence of early-stage disease, but no marker has demonstrated sufficient reliability for clinical application. In the present study, the novel protein EF-hand domain-containing protein D2 (EFHD2) was identified as expressed in highly metastatic tumor cells. EFHD2 increased the formation of protrusive invadopodia structures and cell migration and invasion abilities and promoted the epithelial-to-mesenchymal transition (EMT) character of lung adenocarcinoma cells. We demonstrated that the mechanism of EFHD2 in enhancing EMT occurs partly through inhibition of caveolin-1 (CAV1) for cancer progression. The expression of EFHD2 was significantly correlated with postsurgical recurrence of patients with stage I lung adenocarcinoma in the Kaplan-Meier-plotter cancer database search and our retrospective cohort study (HR, 6.14; 95% CI, 2.40-15.74; P < 0.001). Multivariate Cox regression analysis revealed that EFHD2 expression was an independent clinical predictor for this disease. We conclude that EFHD2 expression is associated with increased metastasis and EMT and could serve as an independent marker to predict postsurgical recurrence of patients with stage I lung adenocarcinoma.

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