探討SLK和ROCK在癌細胞和內皮細胞內的交互作用

Abstract

細胞遷移在生理和疾病上是很重要的，但下游訊息傳遞分子之間的交互作用尚不明瞭。為回答分子之間的交互作用，因此，我們進行”雙擊”集體細胞遷移篩檢。由篩檢結果發現，當細胞同時敲減SLK和抑制ROCK時，集體細胞遷移會有協同增強的表徵。這些結果表示，SLK和ROCK在細胞遷移的過程中有複雜的交互作用。 因此，我們企圖解釋SLK和ROCK之間訊息傳遞的關係。之前的研究暗示，SLK會壓制RhoA活化進而抑制ROCK。然而，我們雙重敲減SLK和RhoA顯示SLK可能不會透過RhoA調控ROCK去改變細胞與細胞之間的協調性。使用HUVEC進行免疫沉澱實驗發現SLK可能與ROCK共同沉澱也更進一步去支持此推測。我們目前正在驗證上述的結果並將會繼續探索SLK和ROCK的交互作用在細胞遷移時的重要功能意義。

Cell migration is important in physiology and diseases, but how signalling molecules interact with each other to control cell migration has remained elusive. We therefore conducted a “two-hit” collective migration screen to answer this question. The screen revealed a synergistic enhancement of collective cell migration when cells were simultaneously treated with SLK knockdown and ROCK inhibition. These results indicate complex interactions between SLK and ROCK during cell migration. We thus aimed at elucidating the signalling relationship between SLK and ROCK. Previous studies suggested that SLK suppressed RhoA activates resulting in ROCK inhibition. However, our RhoA-SLK double knockdown experiment suggested that SLK might regulate ROCK in RhoA-independent manners to alter cell-cell coordination. Thus speculation was further supported by the finding that SLK could be co-immunoprecipitated with ROCK in pulldown assay using HUVEC cells. We are currently verifying the above results and will continue exploring the functional significance of SLK-ROCK interaction during cell migration.