細胞週期與細胞遷移的互話

Abstract

細胞週期(cell cycle)和細胞遷移(cell migration)都是細胞中重要的事件，也都和癌症有相當的關係。當細胞週期受到某些機制影響，如錯誤的紡錘絲排列，就可能造成細胞週期的停滯。當細胞被困在有絲分裂期(mitotic phase)時，週期素(cyclin)的降解也會被抑制，直到所有的機制修復，細胞得以進行正常分裂時，才會再度開始降解週期素，釋放出週期蛋白依賴性激酶(CDK)。在癌症的治療當中，經常使用如長春花生物鹼(vinca alkaloids)、驅動蛋白抑制物(kinesin 5 inhibitors)等小分子藥物造成不正常的紡錘絲排列，將細胞困在有絲分裂期，使得細胞無法分裂，進而殺死細胞。然而過去的研究指出，在這樣的細胞週期停滯下，仍有少量的週期素降解產生，一旦降解的量足夠釋放出週期蛋白依賴性激酶，細胞便得以不需經過正常機制而自行離開有絲分裂期，稱為「脫逃(slippage)」行為。這些逃離有絲分裂期而存活的細胞，就有可能造成癌症治療失敗。在我們的研究中發現，當正常細胞分裂離開有絲分裂期時，也就是剛經過細胞質分裂(cytokinesis)時，會具有較高的遷移能力。這些結果指出細胞進行細胞質分裂與否可能就是影響遷移能力的關鍵。以此推論，這樣的遷移能力一旦經由前述的脫逃行為時，便應當不復存在。因此這些逃離藥物影響而存活的細胞，或許會使這類藥物無法完全的將癌細胞消滅；但另一方面，這些細胞卻因藥物處理失去了遷移能力，得以抑制癌症轉移。

Cell cycle and cell migration are both important events in a cell. Also, they are both important events involved in cancer. When a cell faces some bad situations such as abnormal spindle formation, the cell cycle will be arrested. During mitosis, the arrest is due to the inhibition of cyclin B degradation, and the degradation will restart only when all cellular mechanisms are going well and the cell can undergo normal division, thus release the cyclin-dependent kinase (CDK). In cancer therapies, small molecular drugs like vinca alkaloids and kinesin 5 inhibitors are used to induce the formation of abnormal spindles. This can arrest cells in mitotic phase, and in some cases, eventually kill the cells. Recently, it has been reported that cells under the mitotic arrest can still gradually degrade cyclin B. Once cyclin B level is not enough to maintain high CDK activity, cells will leave the mitotic phase, which is the so-called 'slippage' behavior. These survived cells may result in failed cancer therapies. In our research, we found that unperturbed cells seemed to migrate faster in G1 phase. Moreover, the velocity was greatest right after cytokinesis, then slowed down over the course of the cell cycle. Based on the observation, we hypothesize that cytokinesis may promote the cell migration. When normal cytokinesis was blocked, cells lost this acceleration of migration. Thus, we propose that even though the anti-mitotic drug treatments may not be effective enough in killing some of the cells, these therapies may still have the benefit of suppression cell migration, thus prevent cancer metastasis.