CD24 expression is a marker for predicting clinical outcome and regulates the epithelial-mesenchymal transition in ovarian cancer via both the Akt and ERK pathways.
CD24 expression is a marker for predicting clinical outcome and regulates the epithelial-mesenchymal transition in ovarian cancer via both the Akt and ERK pathways.
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DOI：
10.3892/or.2017.5583
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发表时间：
2017-06
期刊：
影响因子：
4.2
通讯作者：
Ohmichi M
中科院分区：
文献类型：
--
作者：
Nakamura K;Terai Y;Tanabe A;Ono YJ;Hayashi M;Maeda K;Fujiwara S;Ashihara K;Nakamura M;Tanaka Y;Tanaka T;Tsunetoh S;Sasaki H;Ohmichi M
晚期卵巢癌患者的腹膜播散程度和化疗耐药程度与患者的预后有关。上皮-间充质-转化(EMT)是一个多方面的病理过程，赋予癌细胞侵袭和扩散的能力。CD24在多种人类肿瘤中经常过表达，且与不良预后相关。在此，我们检测了CD24在人卵巢癌细胞系中的功能，并评估了它如何通过卵巢癌的EMT机制在肿瘤干细胞(CSCs)再生的分子机制中发挥作用。我们发现70.1%的原发性卵巢癌组织表达CD24，CD24的表达是卵巢癌患者生存的独立预测因素。CD24的表达与FIGO分期、有无腹膜转移和淋巴结转移有关。CD24通过激活PI3K/AKT、NF-κB和ERK，在CAOV-3顺铂耐药细胞株中诱导内皮细胞转化现象，参与细胞侵袭、高增殖表型、集落形成，并与顺铂耐药和CSCs的特性有关。CD24阳性的卵巢癌在体内模型中被证明具有更大的腹内肿瘤细胞扩散的潜力。我们的发现提示CD24在卵巢癌中诱导了EMT现象，CD24通过影响EMT信号通路，通过PI3K/Akt和MAPK通路放大了与细胞生长相关的细胞内信号。我们认为CD24是EMT现象中转移进展的关键分子，也是晚期卵巢癌有希望的治疗靶点。
The degree of peritoneal dissemination and chemotherapy-resistant tumors is related to the prognosis in patients with advanced-stage ovarian cancer. The epithelial-mesenchymal-transition (EMT) is a multifaceted pathological program that endows cancer cells with the ability to invade and disseminate. CD24 is frequently overexpressed in various human cancers and is correlated with a poor prognosis. We herein examined the functions of CD24 in human ovarian cancer cell lines and evaluated how it contributes to the molecular mechanism underlying the regeneration of cancer stem-like cells (CSCs) through the EMT mechanism in ovarian carcinoma. We demonstrated that CD24 was expressed in 70.1% of primary ovarian carcinoma tissues, which were obtained from 174 patients, and that the expression of CD24 was an independent predictor of survival in patients with ovarian cancer. The expression of CD24 has been found to be correlated with the FIGO stage, presence of peritoneal and lymph node metastasis. CD24 induces the EMT phenomenon, which is involved in cell invasion, the highly proliferative phenotype, colony formation and which is associated with cisplatin resistance and the properties of CSCs, via the activation of PI3K/Akt, NF-κB and ERK in Caov-3 cisplatin-resistant cell lines. CD24-positive ovarian carcinomas have been shown to have a greater potential for intra-abdominal tumor cell dissemination in in vivo models. Our findings suggest that CD24 induced the EMT phenomenon in ovarian cancer, and that CD24 amplified cell growth-related intracellular signaling via the PI3K/Akt and MAPK pathways by affecting the EMT signal pathways. We believe that CD24 is a key molecule of metastatic progression in the EMT phenomenon and a promising therapeutic target for advanced ovarian cancer.