PEAK1, acting as a tumor promoter in colorectal cancer, is regulated by the EGFR/KRas signaling axis and miR-181d.
PEAK1, acting as a tumor promoter in colorectal cancer, is regulated by the EGFR/KRas signaling axis and miR-181d.
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PEAK1 在结直肠癌中充当肿瘤启动子，受 EGFR/KRas 信号轴和 miR-181d 调节
DOI：
10.1038/s41419-018-0320-8
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发表时间：
2018-02-15
影响因子：
9
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Huang L;Wen C;Yang X;Lou Q;Wang X;Che J;Chen J;Yang Z;Wu X;Huang M;Lan P;Wang L;Iwamoto A;Wang J;Liu H
PEAK 1在多种人类恶性肿瘤中上调，并与肿瘤侵袭和转移相关，但对PEAK 1在结直肠癌（CRC）进展中的作用知之甚少。我们研究了PEAK 1在结直肠癌中的表达模式、功能及其调控机制。在这里，我们发现PEAK 1在CRC组织中过表达，并且PEAK 1高表达预测结肠癌而不是直肠癌的生存率低。在功能上，沉默PEAK 1在体外抑制细胞增殖、迁移和侵袭，并抑制裸鼠中肿瘤异种移植物的生长。机制研究表明，PEAK 1是由表皮生长因子受体（EGFR）信号转导诱导的，并且PEAK 1是KRas诱导的CRC细胞生长和转移所必需的。此外，我们证明了miR-181 d直接靶向PEAK 1。miR-181 d的异位表达降低了PEAK 1的表达，抑制了大肠癌细胞的生长和转移。临床上，miR-181 d在CRC样本中下调，低miR-181 d与患者生存率低相关。我们的研究证实了PEAK 1在CRC进展中的重要性，并提出了一种潜在的机制，即CRC中PEAK 1表达的增加可能是EGFR/KRas信号激活和随后的miR-181 d抑制的结果。
PEAK1 is upregulated in multiple human malignancies and has been associated with tumor invasion and metastasis, but little is known about the role of PEAK1 in colorectal cancer (CRC) progression. We investigated the expression pattern, function and regulatory mechanisms of PEAK1 in CRC. Here, we found that PEAK1 is overexpressed in CRC tissues and that high PEAK1 expression predicts poor survival in colon cancer but not rectal cancer. Functionally, silencing PEAK1 inhibits cell proliferation, migration, and invasion in vitro and inhibits the growth of tumor xenografts in nude mice. Mechanistic studies revealed that PEAK1 is induced by epidermal growth factor receptor (EGFR) signaling and that PEAK1 is required for KRas-induced CRC cell growth and metastasis. Furthermore, we demonstrated that miR-181d directly targets PEAK1. Ectopic expression of miR-181d reduces the expression of PEAK1 and inhibits the growth and metastasis of CRC cells in vitro. Clinically, miR-181d is downregulated in CRC samples, and low miR-181d is correlated with poor patient survival. Our study demonstrates the importance of PEAK1 in CRC progression and suggests a potential mechanism by which increasing PEAK1 expression in CRC might be the result of EGFR/KRas signal activation and consequent miR-181d repression.
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影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
4.7
作者：
Leto, Simonetta M.;Trusolino, Livio
通讯作者：
Trusolino, Livio
MAP4K4 是肺腺癌维持所需的新型 MAPK/ERK 通路调节因子
影响因子：
6.6
作者：
Gao X;Chen G;Gao C;Zhang DH;Kuan SF;Stabile LP;Liu G;Hu J
通讯作者：
Hu J
影响因子：
24.5
作者：
Hur K;Toiyama Y;Takahashi M;Balaguer F;Nagasaka T;Koike J;Hemmi H;Koi M;Boland CR;Goel A
通讯作者：
Goel A
影响因子：
24.5
作者：
Han TS;Hur K;Xu G;Choi B;Okugawa Y;Toiyama Y;Oshima H;Oshima M;Lee HJ;Kim VN;Chang AN;Goel A;Yang HK
通讯作者：
Yang HK