Jiang Yongsheng, Sun Shaochuan, Liu Guoqin, Yan Bing, Niu Jun
Department of General Surgery, Jinan Central Hospital, Shandong University, Jinan, 250013, China.
Tumour Biol. 2015 Feb;36(2):1129-33. doi: 10.1007/s13277-014-2726-y. Epub 2014 Oct 21.
The molecular mechanism underlying cancer invasiveness and metastasis of colorectal cancer (CRC) remains elusive. Here we reported a strong correlation of the levels of neuregulin receptor degradation protein-1 (Nrdp1) and matrix metalloproteinase-7 (MMP7) in CRC from the patients. We then used a human CRC line, Caco-2, to study the underlying molecular basis. We found that Nrdp1 inhibited the phosphorylation of ErB3, a key player in epidermal growth factor receptor (EGFR) signaling in Caco-2 cells, which is required for activation of MMP7 to promote cell invasion. Our findings thus reveal Nrdp1, EGFR signaling, and MMP7 as promising therapeutic targets for preventing the metastasis of CRC.
结直肠癌（CRC）侵袭和转移的分子机制仍不清楚。在此，我们报告了患者结直肠癌中神经调节蛋白受体降解蛋白-1（Nrdp1）和基质金属蛋白酶-7（MMP7）水平之间存在强相关性。然后，我们使用人结直肠癌细胞系Caco-2来研究潜在的分子基础。我们发现，Nrdp1抑制了Caco-2细胞中表皮生长因子受体（EGFR）信号传导的关键因子ErB3的磷酸化，而ErB3的磷酸化是激活MMP7以促进细胞侵袭所必需的。因此，我们的研究结果揭示了Nrdp1、EGFR信号传导和MMP7是预防结直肠癌转移的有前景的治疗靶点。
