肺癌是全球最常見的惡性腫瘤之一，治療過程中失巢抗性是治療效果不佳的一個重要因素。因此，深入了解失巢抗性的機制，尋找新的治療標靶，對提高肺癌治療效果具有重要意義。首先，我們在TCGA與CPTAC的資料庫分析後發現CD44與ESRP1在癌症發展中占有重要角色。我們挑選了三種肺癌細胞H1299、A549與PC9發現其在懸浮培養時的生存型態差異與細胞週期，前兩者的細胞凋亡SubG1會顯著上升。發現H1299與A549的懸浮型細胞Malat1 mRNA表現量相比貼附型細胞增加，而PC9則相反。ESRP1則是PC9的懸浮型細胞表現量相比增加，而H1299及A549則相反。此外，我們發現PC9在生長時同時具有貼附與懸浮型細胞，在傷口癒合能力實驗中發現讓其快速癒合的為懸浮型細胞，且其細胞可以在多代數的培養下持續加速生長，且在細胞遷移能力也比貼附型態的細胞能力更好。在失巢凋亡的實驗中發現H1299與A549在24小時的培養後會死亡，而PC9會上升，進一步在CD44的蛋白表現中發現，兩者的CD44整體表現量下降，而PC9的則上升。此外發現CD44v6-10與v8-10的兩個變異型存在於PC9失巢凋亡的環境下。CD44變異型可能在這些過程中扮演著不同的角色，特別是與失巢抗性相關的機制。研究CD44變異型在肺癌中的表現和功能，有助於深入瞭解這種變異對失巢抗性的調控機制。

Lung cancer is one of the most common malignant tumors globally, and resistance to anoikis during the treatment process is a significant factor contributing to poor therapeutic outcomes. Therefore, gaining a deep understanding of the mechanisms underlying anoikis resistance and identifying new therapeutic targets holds crucial significance for enhancing the efficacy of lung cancer treatment. In our study, TCGA and CPTAC analyses identified CD44 and ESRP1 pivotal roles in cancer development. In H1299, A549, and PC9 lung cancer cell lines, suspended culture showed distinct survival and cell cycle differences. Notably, SubG1 apoptotic cells increased in H1299 and A549. Malat1 mRNA in suspended H1299 and A549 cells was higher than adherent cells, while the opposite trend occurred in PC9. ESRP1 expression increased in suspended PC9 cells but decreased in H1299 and A549. Furthermore, PC9 exhibited simultaneous adherent and suspended cell type, the suspended type accelerated wound closure, and superior migration ability. Anoikis resistance experiments revealed H1299 and A549 cell death after 24 hours, while PC9 increased survival. CD44 protein analysis indicated decreased expression in H1299 and A549, contrasting with an increase in PC9. Additionally, we identified two CD44 variant isoforms, CD44v6-10 and v8-10, in PC9's anoikis-resistant environment. The existence of CD44 variants suggests their potential involvement in different roles, particularly in mechanisms associated with anoikis resistance. Investigating the expression and function of CD44 variants in lung cancer contributes to a deeper understanding of how these variations regulate anoikis resistance mechanisms.

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