Author(s): Chou TY, Chen WC, Lee AC, Hung SM, Shih NY, et al.
The ubiquitously expressed glycoprotein Clusterin (CLU) is implicated in diverse cellular processes, yet its genuine molecular function remains undefined. CLU expression has been associated with various human malignancies, yet the mechanisms by which CLU promotes cancer progression and metastasis are not elucidated. In this study, using human lung adenocarcinoma cell lines as a model, we explored the involvement of CLU in modulating invasiveness of cancer cells. We discovered that CLU levels positively correlated with the degree of invasiveness in human lung adenocarcinoma cell lines. The observation that CLU-rich cells displayed a spindle-shape morphology while those with low CLU levels were cuboidal in shape prompted us to investigate if CLU modulates epithelial-to-mesenchymal transitions (EMT). CLU silencing by siRNA in a highly invasive, CLU-rich lung adenocarcinoma cell line induced a mesenchymal-to-epithelial transition (MET) evidenced by the spindle-to-cuboidal morphological change, increased E-cadherin expression, and decreased fibronectin expression. Compared with the vector-transfected cells, CLU-knocked-down (CLUi) cells showed reduced migration and invasion in vitro, as well as decreased metastatic potential in experimental metastasis. Re-expression of CLU in CLUi cells reversed the MET and restored the mesenchymal and invasive phenotypes. We found that Slug, a zinc-finger-containing transcriptional repressor of E-cadherin, was downregulated in CLUi cells. We also discovered that levels of activated ERK correlated with those of CLU and Slug. Taken together, our data suggest that CLU may regulate EMT and aggressive behaviour of human lung adenocarcinoma cells through modulating ERK signalling and Slug expression.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/19166932
Author(s): Neal JW, Gubens MA, Wakelee HA
Author(s): Chang A
Author(s): Kartalou M, Essigmann JM
Author(s): Rabik CA, Dolan ME
Author(s): Siddik ZH
Author(s): Rosenberg ME, Silkensen J
Author(s): Niu ZH, Wang Y, Chun B, Li CX, Wu L
Author(s): Zoubeidi A, Chi K, Gleave M
Author(s): Yang GF, Li XM, Xie D
Author(s): He LR, Liu MZ, Li BK, Rao HL, Liao YJ, et al.
Author(s): Xie MJ, Motoo Y, Su SB, Mouri H, Ohtsubo K, et al.
Author(s): Park DC, Yeo SG, Wilson MR, Yerbury JJ, Kwong J, et al.
Author(s): Wang Y, Wang X, Zhao H, Liang B, Du Q
Author(s): Yan Y, Luo K, Zhang H, Chai W
Author(s): Cheng CY, Cherng SH, Wu WJ, Yang TY, Huang XY, et al.
Author(s): Laskin JJ, Nicholas G, Lee C, Gitlitz B, Vincent M, et al.
Author(s): Cao C, Shinohara ET, Li H, Niermann KJ, Kim KW, et al.
Author(s): Bortul R, Tazzari PL, Billi AM, Tabellini G, Mantovani I, et al.
Author(s): Liu D, Zhang Y, Dang C, Ma Q, Lee W, et al.
Author(s): Guinea Viniegra J, HernÃ¡ndez Losa J, SÃ¡nchez-ArÃ©valo VJ, ParadaCobo C, FernÃ¡ndezSoria VM, et al.
Author(s): McCubrey JA, Steelman LS, Abrams SL, Lee JT, Chang F, et al.
Author(s): McCubrey JA, Steelman LS, Chappell WH, Abrams SL, Wong EW, et al.
Author(s): Sridhar SS, Hedley D, Siu LL
Author(s): Tang Y, Liu F, Zheng C, Sun S, Jiang Y
Author(s): Si H, Peng C, Li J, Wang X, Zhai L, et al.
Author(s): Zhou L, Luan H, Liu Q, Jiang T, Liang H, et al.
Author(s): Li H, Schmid-Bindert G, Wang D, Zhao Y, Yang X, et al.
Author(s): Lee HY, Oh SH, Suh YA, Baek JH, Papadimitrakopoulou V, et al.
Author(s): Wang M, Liu ZM, Li XC, Yao YT, Yin ZX
Author(s): Li J, Jia L, Zhao P, Jiang Y, Zhong S, et al.
Author(s): Xiu P, Dong X, Dong X, Xu Z, Zhu H, et al.
Author(s): Ma X, Bai Y
Author(s): Scaltriti M, Bettuzzi S, Sharrard RM, Caporali A, Caccamo AE, et al.
Author(s): Manic S, Gatti L, Carenini N, Fumagalli G, Zunino F, et al.
Author(s): Springate CM, Jackson JK, Gleave ME, Burt HM
Author(s): Miyake H, Hara S, Zellweger T, Kamidono S, Gleave ME, et al.
Author(s): Hoeller C, Pratscher B, Thallinger C, Winter D, Fink D, et al.
Author(s): Redondo M, TÃ©llez T, Roldan MJ, Serrano A, GarcÃa-Aranda M, et al.
Author(s): Lourda M, Trougakos IP, Gonos ES
Author(s): Karaca B, Atmaca H, Bozkurt E, Kisim A, Uzunoglu S, et al.
Author(s): Pajak B, Orzechowski A
Author(s): Peyssonnaux C, EychÃ¨ne A
Author(s): Zhuang S, Schnellmann RG
Author(s): Ko JC, Tsai MS, Chiu YF, Weng SH, Kuo YH, et al.
Author(s): Gozdz A, Habas A, Jaworski J, Zielinska M, Albrecht J, et al.
Author(s): Huang WC, Hung MC
Author(s): Seo JH, Jeong ES, Lee KS, Heo SH, Jeong DG, et al.