Ueda Masami, Iguchi Tomohiro, Masuda Takaaki, Komatsu Hisateru, Nambara Sho, Sakimura Shotaro, Hirata Hidenari, Uchi Ryutaro, Eguchi Hidetoshi, Ito Shuhei, Sugimachi Keishi, Mizushima Tsunekazu, Doki Yuichiro, Mori Masaki, Mimori Koshi
Department of Surgery, Kyushu University Beppu Hospital, Beppu, Japan.
Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
Anticancer Res. 2017 May;37(5):2255-2263. doi: 10.21873/anticanres.11562.
BACKGROUND/AIM: SLC9A9 plays an oncogenic role in esophageal squamous carcinoma and glioblastoma. Herein, we showed an oncogenic function of SLC9A9 in colorectal cancer (CRC).
We examined SLC9A9 expression in CRC specimens by immunohistochemistry. In CRC tissues, the relationship between SLC9A9 expression and clinicopathological factors was further elucidated by quantitative real-time polymerase chain reaction (qRT-PCR) and gene set enrichment analysis (GSEA). In vitro, we performed knockdown and overexpression experiments.
SLC9A9 was overexpressed in CRC specimens. In clinicopathological analysis of our cohort, high SLC9A9 expression increased liver metastasis and was correlated with worse prognoses in two cohorts. A significantly positive relationship between SLC9A9 and EGFR was revealed. While knockdown of SLC9A9 suppressed proliferation and anchorage-independent growth, up-regulation of SLC9A9 promoted proliferation and anchorage-independent growth in vitro.
SLC9A9 has an oncogenic function by being related to EGFR signaling, suggesting SLC9A9 may be a novel prognostic indicator and a therapeutic target in CRC.
背景/目的:SLC9A9在食管鳞状细胞癌和胶质母细胞瘤中发挥致癌作用。在此,我们展示了SLC9A9在结直肠癌(CRC)中的致癌功能。
我们通过免疫组织化学检测了结直肠癌标本中SLC9A9的表达。在结直肠癌组织中,通过定量实时聚合酶链反应(qRT-PCR)和基因集富集分析(GSEA)进一步阐明了SLC9A9表达与临床病理因素之间的关系。在体外,我们进行了敲低和过表达实验。
SLC9A9在结直肠癌标本中过表达。在我们队列的临床病理分析中,高SLC9A9表达增加了肝转移,并且在两个队列中与较差的预后相关。揭示了SLC9A9与EGFR之间存在显著的正相关关系。虽然敲低SLC9A9可抑制增殖和非锚定依赖性生长,但SLC9A9的上调在体外促进了增殖和非锚定依赖性生长。
SLC9A9通过与EGFR信号传导相关而具有致癌功能,提示SLC9A9可能是结直肠癌中一种新的预后指标和治疗靶点。