乙醛脱氢酶1(ALDH1)阳性的肺癌干细胞具有较强的致瘤性和侵袭性，是肺癌难以治愈的原因之一。CD98蛋白重链(CD98hc)在肺癌组织中高表达并调控肺癌细胞的增殖和侵袭。但是CD98hc对ALDH1阳性肺癌干细胞的作用尚不明确。我们前期研究发现肺癌组织CD98hc与ALDH1A3含量呈正相关。敲低肺腺癌细胞A549中CD98hc表达导致鞘脂合成途径重要产物1-磷酸鞘氨醇(S1P)分泌减少伴随ALDH1表达降低。而A549细胞在S1P单独作用下ALDH1活性增强。由此我们提出“CD98蛋白重链通过调控鞘脂合成代谢维持ALDH1阳性肺癌干细胞增殖和转移”这一科学命题。本项目拟检测CD98hc对ALDH1阳性肺癌干细胞增殖和侵袭的调控作用，着重分析CD98hc通过鞘脂代谢影响ALDH1阳性肺癌干细胞“干性”的机制。本项目将阐明CD98hc影响ALDH1活性的机制，为肺癌治疗提供新的分子靶点。

Aldehyde dehydrogenase 1 (ALDH1) positive lung cancer stem cells have strong tumorigenicity and invasiveness, which is one of the reasons why lung cancer is difficult to cure. CD98 protein heavy chain (CD98hc) is highly expressed in lung cancer tissues and regulates the proliferation and invasion of lung cancer cells. However, the effect of CD98hc on ALDH1 positive lung cancer stem cells remains unclear. Our previous studies found that there was a positive correlation between CD98hc and ALDH1A3 in lung cancer tissues. Knocking down the expression of CD98hc in lung adenocarcinoma cell line A549 resulted in a decrease of sphingosine phosphate (S1P) secretion, an important product of sphingolipid biosynthesis pathway, accompanied by a decrease of ALDH1 expression. However, the activity of ALDH1 in A549 cells increased under the action of S1P alone. Therefore, we propose the scientific proposition that CD98 protein heavy chain can maintain proliferation and metastasis of ALDH1 positive lung cancer stem cells by regulating sphingolipid metabolism. This project intends to detect the regulatory effect of CD98hc on proliferation and invasion of ALDH1 positive lung cancer stem cells, focusing on the mechanism of CD98hc affecting the stemness of ALDH1 positive lung cancer stem cells through sphingolipid metabolism. This project will elucidate the mechanism of CD98hc affecting ALDH1 activity and provide a new molecular target for lung cancer treatment.