Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, People's Republic of China.
Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
J Exp Clin Cancer Res. 2019 Jul 9;38(1):296. doi: 10.1186/s13046-019-1290-0.
Karyopherin nuclear transport receptors play important roles in tumour development and drug resistance and have been reported as potential biomarkers and therapeutic targets for tumour treatment. However, IPO5, one of the karyopherin nuclear transport receptor family members, remains largely uncharacterized in tumour progression.
The TCGA data, quantitative reverse transcription-PCR (qRT-PCR), western blotting, and IHC analyses were used to detect IPO5 expression in CRC tissues. A series of in vivo and in vitro experiments was utilized to demonstrate the function of IPO5 in CRC tissues. Mass spectrometry (MS), CO-IP technology, subcellular fractionation, and immunofluorescence were utilized to investigate the possible mechanisms of CRC.
IPO5 was highly expressed and positively correlated with the clinicopathological characteristics of colorectal cancer tissues. Functional experiments indicated that IPO5 could promote the development of CRC. Mechanistically, we screened RASAL2, one cargo of IPO5, and further confirmed that IPO5 bound to the NLS sequence of RASAL2, mediating RASAL2 nuclear translocation and inducing RAS signal activation, thereby promoting the progression of CRC.
Together, our results indicate that IPO5 is overexpressed in colorectal cancer cells. By transporting RASAL2, IPO5 may play a crucial role in CRC.
核孔蛋白核转运受体在肿瘤的发生和耐药中发挥重要作用，已被报道为肿瘤治疗的潜在生物标志物和治疗靶点。然而，核孔蛋白核转运受体家族的一员 IPO5 在肿瘤进展中仍然很大程度上没有被描述。
利用 TCGA 数据、定量逆转录-PCR（qRT-PCR）、western blot 和 IHC 分析检测 CRC 组织中 IPO5 的表达。利用一系列体内和体外实验证明 IPO5 在 CRC 组织中的功能。利用质谱（MS）、CO-IP 技术、亚细胞分馏和免疫荧光技术研究 CRC 的可能机制。
IPO5 在结直肠癌组织中高表达，并与临床病理特征呈正相关。功能实验表明，IPO5 可以促进 CRC 的发展。机制上，我们筛选出 IPO5 的一个货物 RASAL2，并进一步证实 IPO5 与 RASAL2 的 NLS 序列结合，介导 RASAL2 核转位并激活 RAS 信号，从而促进 CRC 的进展。
综上所述，我们的结果表明 IPO5 在结直肠癌细胞中过度表达。通过运输 RASAL2，IPO5 可能在 CRC 中发挥关键作用。
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