在Myc觸發的細胞競爭中JAK-STAT會高度活化並淘汰失去競爭力的細胞

JAK-STAT is Hyper-Activated and Unusually Mediates the Loser Elimination in Myc-Induced Cell Competition

江致瑩(Chih-Ying Chiang)

指導教授 ： 黃敏郎

國立中正大學/理學院/生命科學系生物醫學研究所/碩士(2015年)

摘要

細胞競爭 (Cell competition) 是在同一組織內會出現的現象，競爭力強的細胞 (Winner cell) 會淘汰並取代競爭力弱的細胞 (Loser cell)，這是一個從果蠅到哺乳類演化上都高度保留的機制，這機制參與器官大小的控制以及腫瘤的形成與抑制 (tumorigenesis)，在多數的情況下Winner cell和Loser cell的生長、增生及蛋白質的轉譯能力都有所差別。Myc和JAK-STAT在多細胞生物的演化上同樣是高度保留的，並且對於細胞的生長與發育都很重要，當細胞缺乏Myc或是JAK-STAT的時候，會導致細胞競爭的發生，缺乏Myc或是JAK-STAT的細胞會被周圍正常細胞 (WT cell) 給淘汰掉，先前研究指出Myc和JAK-STAT在細胞競爭的機制是互相獨立的，但有趣的是，我們發現在MycRi所導致的細胞競爭中，STAT的轉錄活性會被活化，並且當JAK-STAT的components表現量減少時，MycRi clone的變小的現象會被拯救回來，在這裡我們主要的是探討在細胞競爭中，Myc和JAK-STAT之間的關係，我們利用Flip-out-GAL4-UAS system去量化細胞競爭的程度，我們的結果顯示，在Myc所導致的細胞競爭中是需要JAK-STAT活性的，也說明了在細胞競爭中Myc有能力去調控JAK-STAT的活性，綜合我們實驗的結果，我們認為Myc所導致的細胞競爭中，Myc會調控JAK-STAT的活性且STAT的活化會導致細胞被淘汰。

關鍵字

細胞競爭

並列摘要

Cell competition is a phenomenon, where the optimal cells (winner) eliminate and replace suboptimal cells (loser) in the same tissue. Cell competition is an evolutionarily conserved mechanism from Drosophila to mammals, and it is involved in organ size regulation and tumorigenesis. In most cases of cell competition, winner and loser cells are different in cell growth, proliferation, and protein translation. Myc and JAK-STAT signaling pathway are evolutionarily conserved in multicellular organisms and also critical in cell growth and development. When a cell is deprived of JAK-STAT or Myc, it becomes a loser eliminated by surrounding WT cell. A previous study indicated that Myc and JAK-STAT are independent in cell competition. Intriguingly, we found that in MycRi-induced cell competition, STAT transcription is activated and down-regulation of JAK-STAT components rescue the clone size. Here, we focus on the relationship between three JAK-STAT components (Domeless, Hop and STAT92E) and Myc. We use Flip-out-GAL4-UAS system to quantitate the degree of cell competition and represent significant data regarding the role of JAK-STAT and Myc in cell competition. Our results demonstrate that STAT activity is required for Myc-induced cell competition. Myc may modulate STAT signaling activity in cell competition. Taken together, we consider that STAT activity is harmful and modulated by Myc in Myc-induced cell competition.

並列關鍵字

cell competition ； Myc ； STAT

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