Upregulation of metastasis-associated PRL-3 initiates chordoma in zebrafish.
Upregulation of metastasis-associated PRL-3 initiates chordoma in zebrafish.
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DOI：
10.3892/ijo.2016.3363
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发表时间：
2016-04
影响因子：
5.2
通讯作者：
Li Li-Li;Hongshun Shi;Mingming Zhang;Xiaoling Guo;Fang Tong;Wenlian Zhang;Junyi Zhou;Haihe Wang;Shulan Yang
中科院分区：
文献类型：
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作者：
Li Li-Li;Hongshun Shi;Mingming Zhang;Xiaoling Guo;Fang Tong;Wenlian Zhang;Junyi Zhou;Haihe Wang;Shulan Yang
再生肝转移相关磷酸酶-3(PRL-3)在多种人类肿瘤的发生发展中发挥多种作用，但其在肿瘤发生发展过程中的作用意义尚未阐明。在这里，我们克隆和鉴定了斑马鱼PRL-3转录本的表达模式，结果表明，它在发育的前24小时普遍表达，既有母体表达，也有受精卵表达。受精后96h，转录物逐渐局限于脊索、血管和肠道。值得注意的是，斑马鱼PRL-3(zPrl-3)和人PRL-3的过表达会诱导斑马鱼的脊索畸形。这种表型类似于脊索瘤，并被脊索特异性标志物的相关错误表达所证实。通过对临床脊索瘤标本中PRL-3抗原的检测，强烈提示了脊索瘤PRL-3的临床意义。总之，我们的结果发现PRL-3的异常过表达可以在脊索瘤的早期发展中启动，并提示PRL-3的使用可以作为脊索瘤的预测指标和治疗靶点。
The metastasis-associated phosphatase of regenerating liver-3 (PRL-3) plays multiple roles in progression of various human cancers; however, significance of its role during development has not been addressed. Here we cloned and characterized the expression pattern of zebrafish prl-3 transcript and showed that it is ubiquitiously expressed in the first 24 h of development with both maternal and zygotic expressions. The transcripts become progressively restricted to the notochord, vessels and the intestine by 96 h post-fertilization. Notably, overexpression of zebrafish Prl-3 (zPrl-3) and human PRL-3 induces notochord malformation in zebrafish. This phenotype resembles chordoma and is confirmed by associated misexpression of notochord-specific markers. Clinical significance of the PRL-3 in chordoma is strongly suggested by detection of PRL-3 antigen in clinical chordoma specimens. Collectively, our results uncovered that aberrant overexpression of PRL-3 could initiate chordoma in early development and suggest the use of PRL-3 could be used as a predictor and a therapeutic target for chordoma.