PBX3 promotes migration and invasion of colorectal cancer cells via activation of MAPK/ERK signaling pathway
PBX3 promotes migration and invasion of colorectal cancer cells via activation of MAPK/ERK signaling pathway
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PBX3通过激活MAPK/ERK信号通路促进结直肠癌细胞迁移和侵袭
DOI：
10.3748/wjg.v20.i48.18260
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发表时间：
2014-12-28
影响因子：
4.3
通讯作者：
Zhang, Zhi-Qian
中科院分区：
文献类型：
--
作者：
Han, Hai-Bo;Gu, Jin;Zhang, Zhi-Qian
目的：为探讨前B细胞白血病同源框3（pre-B-cellleukemiahomeobox，PBX 3）在结直肠癌细胞迁移和侵袭中的作用，采用实时荧光定量逆转录聚合酶链反应（real-timeRT-PCR）技术检测了5种结直肠癌细胞系和111例结直肠癌手术标本中PBX 3的表达。我们在低转移性HT-29和SW 480细胞中强制表达PBX 3，并在高转移性LOVO和HCT-8细胞中敲低PBX 3的表达。伤口愈合和Boyden室测定用于检测PBX 3表达改变后的细胞迁移和侵袭。Western blot检测PBX 3过表达后细胞内信号分子ERK 1/2的变化。高水平的PBX 3表达与大肠癌细胞的侵袭能力相关，并与淋巴结侵袭显著相关（P = 0.02）、远处转移（P = 0.04）、TNM分期高（P = 0.03）、总生存率低（P < 0.05）。在低转移细胞中异位表达PBX 3可促进迁移和侵袭，而在高转移细胞中抑制PBX 3表达可抑制迁移和侵袭。结论：PBX 3通过激活MAPK/ERK信号通路诱导结直肠癌细胞的侵袭和转移。
AIM: To investigate the role of pre-B-cell leukemia homeobox (PBX) 3 in migration and invasion of colorectal cancer (CRC) cells.METHODS: We detected PBX3 expression in five cell lines and surgical specimens from 111 patients with CRC using real-time reverse transcription-polymerase chain reaction. We forced expression of PBX3 in low metastatic HT-29 and SW480 cells and knocked down expression of PBX3 in highly metastatic LOVO and HCT-8 cells. Wound healing and Boyden chamber assays were used to detect cell migration and invasion after altered expression of PBX3. Western blot was performed to detect the change of signaling molecule ERK1/2 following PBX3 overexpression.RESULTS: High level of PBX3 expression was correlated with the invasive potential of CRC cells, and significantly associated with lymph node invasion (P = 0.02), distant metastasis (P = 0.04), advanced TNM stage (P = 0.03) and poor overall survival of patients (P < 0.05). Ectopic expression of PBX3 in low metastatic cells was shown to promote migration and invasion, while inhibited PBX3 expression in highly metastatic cells suppressed migration and invasion. Furthermore, upregulation of phosphorylated extracellular signal-regulated kinase (ERK) 1/2 was found to be one of the targeted molecules responsible for PBX3-induced CRC cell migration and invasion.CONCLUSION: PBX3 induces invasion and metastasis of CRC cells partially through activation of the MAPK/ERK signaling pathway.