探討Collapsin Response Mediator Protein 1 (CRMP-1) 及 Capping Protein G (CapG) 在肺癌轉移所扮演的角色

The Role of Collapsin Response Mediator Protein 1 (CRMP-1) and Capping Protein G (CapG) in Lung Cancer Metastasis

楊佩珊(Ieong Pui San)

指導教授 ： 周綠蘋

共同指導教授 ： 楊泮池(Pan-Chyr Yang)

國立臺灣大學/醫學院/生物化學暨分子生物學研究所/碩士(2006年)

https://doi.org/10.6342/NTU.2006.10325

摘要

癌轉移是癌症病患癒後良好與否的一項關鍵決定因子，是以如何有效地阻止癌轉移的發生，便成為治療癌症病人的一個重要研究方向。本實驗室利用腺癌細胞株成功地發現 collapsin response mediator protein-1 ( CRMP-1 ) 為一個抑制癌侵襲的基因，此蛋白質會導致絲狀偽足的肌動蛋白纖維去聚合化，進而減緩癌細胞之侵襲能力；雖然肌動蛋白纖維的聚合化與神經軸突生長及癌細胞的侵襲有著重要的關係，但 CRMP-1 如何導致肌動蛋白去聚合化的機制並不清楚。為了找尋被 CRMP-1調控並與侵襲有關的蛋白質群體，我們利用二維電泳分離蛋白技術，將過度表現 CRMP-1 的細胞及其控制組細胞的總蛋白分離並比較其蛋白質表現圖譜。結果發現Capping protein G ( CapG )，Capping protein muscle Z-lineβsubunit ( CapZB )及 TAT binding protein 1 ( TBP-1 ) 這三個蛋白質之表現量受 CRMP-1所調控。進一步研究指出CapG 與細胞侵襲及病人死亡率有正相關性，同時CapG 與促進侵襲基因 LCRMP-1 有交互作用，這兩個蛋白質會同時存在於細胞的絲狀偽足的頂端及在細胞邊緣的片狀偽足上，因此他們可能在細胞侵襲上共同作用。總括來說，我們發現CapG 參與 LCRMP-1 促進細胞侵襲的機制中，並且CapG 的表現量會受到癌轉移抑制基因 CRMP-1 所調控。

關鍵字

肺癌

並列摘要

Patients with metastasis have poor prognosis. Preventing invasion, the crucial step of metastasis is a good strategy for cancer therapy. Recently, we discovered that collapsin response mediator protein-1 (CRMP-1) is a novel invasion suppressor gene in lung adenocarcinoma. CRMP-1 is a protein that leads depolymerization of filopodial actin filament, it is interesting that polymerization of actin filament is essential for axon growth as well as cancer cell invasion, but the mechanism is not clear.　To explore invasion-association proteins regulated by CRMP-1, we compared the protein profile from control and over-expressed CRMP-1 in CL1-5 by 2-dimensional (2DE) gel electrophoresis protein separation. Three proteins were down-regulated when overexpressed CRMP-1, they are capping protein G (CapG), capping protein muscle Z-line β subunit (CapZB) and Tat binding protein 1 (TBP-1).We found that CapG is positively related to invasion in vitro and negatively related to patient’s survival. An isoform of CRMP-1, LCRMP-1, is an invasion promoting gene, which interacts with CapG and colocalized at the tip of filopdoia and lamellipodia. CapG and LCRMP-1 may cocontribute the ability of cell invasion. In conclusion, we discovered that CapG involved in LCRMP-1 promoted invasion and its expression is down regulated by CRMP-1.

並列關鍵字

CRMP-1 ； CapG

參考文獻

Reference List)

Aizawa,H., Wakatsuki,S., Ishii,A., Moriyama,K., Sasaki,Y., Ohashi,K., Sekine-Aizawa,Y., Sehara-Fujisawa,A., Mizuno,K., Goshima,Y., and Yahara,I. (2001). Phosphorylation of cofilin by LIM-kinase is necessary for semaphorin 3A-induced growth cone collapse. Nat. Neurosci. 4, 367-373.

Bahassi,E.M., Karyala,S., Tomlinson,C.R., Sartor,M.A., Medvedovic,M., and Hennigan,R.F. (2004). Critical regulation of genes for tumor cell migration by AP-1. Clin. Exp. Meta. 21, 293-304.

Barak,O., Aronheim,A., and Shaul,Y. (2001). HBV X protein targets HIV Tat-binding protein 1. Virology 283, 110-120.

Barzik,M., Kotova,T.I., Higgs,H.N., Hazelwood,L., Hanein,D., Gertler,F.B., and Schafer,D.A. (2005). Ena/VASP proteins enhance actin polymerization in the presence of barbed end capping proteins. J. Biol. Chem. 280, 28653-28662.