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CD24表达是预测临床结果的标志物,并通过Akt和ERK途径调节卵巢癌中的上皮-间质转化。

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.

作者信息

Nakamura Kiyoko, Terai Yoshito, Tanabe Akiko, Ono Yoshihiro J, Hayashi Masami, Maeda Kazuya, Fujiwara Satoe, Ashihara Keisuke, Nakamura Michihiko, Tanaka Yoshimichi, Tanaka Tomohito, Tsunetoh Satoshi, Sasaki Hiroshi, Ohmichi Masahide

机构信息

Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki-city, Osaka 569-8686, Japan.

出版信息

Oncol Rep. 2017 Jun;37(6):3189-3200. doi: 10.3892/or.2017.5583. Epub 2017 Apr 19.

Abstract

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.

摘要

腹膜播散程度和化疗耐药性肿瘤与晚期卵巢癌患者的预后相关。上皮-间质转化(EMT)是一个多方面的病理过程,赋予癌细胞侵袭和播散的能力。CD24在多种人类癌症中经常过度表达,且与预后不良相关。我们在此研究了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中的EMT机制促成癌症干细胞(CSC)再生的分子机制。我们证明,在从174例患者获取的原发性卵巢癌组织中,70.1%表达CD24,且CD24的表达是卵巢癌患者生存的独立预测指标。已发现CD24的表达与国际妇产科联盟(FIGO)分期、腹膜和淋巴结转移的存在相关。在Caov-3顺铂耐药细胞系中,CD24通过激活PI3K/Akt、NF-κB和ERK诱导EMT现象,该现象涉及细胞侵袭、高增殖表型、集落形成,且与顺铂耐药及CSC特性相关。在体内模型中,CD24阳性的卵巢癌已显示出更大的腹腔内肿瘤细胞播散潜力。我们的研究结果表明,CD24在卵巢癌中诱导EMT现象,且CD24通过影响EMT信号通路,经由PI3K/Akt和MAPK途径放大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,也是晚期卵巢癌有前景的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81c7/5442399/0d1391449267/OR-37-06-3189-g00.jpg

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