Low molecular weight protein tyrosine phosphatase (LMWPTP) upregulation mediates malignant potential in colorectal cancer.
Low molecular weight protein tyrosine phosphatase (LMWPTP) upregulation mediates malignant potential in colorectal cancer.
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低分子量蛋白酪氨酸磷酸酶（LMWPTP）上调介导结直肠癌的恶性潜力。
DOI：
10.18632/oncotarget.3224
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发表时间：
2015-04-10
期刊：
影响因子：
--
通讯作者：
Fuhler GM
中科院分区：
文献类型：
--
作者：
Hoekstra E;Kodach LL;Das AM;Ruela-de-Sousa RR;Ferreira CV;Hardwick JC;van der Woude CJ;Peppelenbosch MP;Ten Hagen TL;Fuhler GM
长期以来，磷酸酶一直被认为是肿瘤抑制因子，然而，越来越多的证据表明，某些磷酸酶在几种形式的癌症中起肿瘤启动作用。低分子量蛋白酪氨酸磷酸酶（Low Molecular Weight Protein Tyrosine Phosphatase， LMWPTP; acid Phosphatase 1 [ACP1]）是一种18 kDa的酶，可影响与癌症相关的信号通路介质的磷酸化，因此被认为是一种促肿瘤酶，但目前还没有明确的临床证据，也没有确定LMWPTP作用的令人信服的机制作用。在本研究中，我们发现LMWPTP的表达不仅在结直肠癌（CRC）中显著增加，而且在不同程度的不典型增生中也会逐步增加。化学抑制LMWPTP可显著降低结直肠癌的生长。此外，CRC中LMWPTP的下调导致2D和3d迁移测试中的迁移能力降低，并使肿瘤细胞对化疗药物5-FU敏感。综上所述，本研究表明LMWPTP不仅在结直肠癌中过表达，而且与结直肠癌的恶性潜能相关，提示该磷酸酶可能作为结直肠癌分期的预测生物标志物，是治疗结直肠癌的合理新靶点。
Phosphatases have long been regarded as tumor suppressors, however there is emerging evidence for a tumor initiating role for some phosphatases in several forms of cancer. Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP; acid phosphatase 1 [ACP1]) is an 18 kDa enzyme that influences the phosphorylation of signaling pathway mediators involved in cancer and is thus postulated to be a tumor-promoting enzyme, but neither unequivocal clinical evidence nor convincing mechanistic actions for a role of LMWPTP have been identified. In the present study, we show that LMWPTP expression is not only significantly increased in colorectal cancer (CRC), but also follows a step-wise increase in different levels of dysplasia. Chemical inhibition of LMWPTP significantly reduces CRC growth. Furthermore, downregulation of LMWPTP in CRC leads to a reduced migration ability in both 2D- and 3D-migration assays, and sensitizes tumor cells to the chemotherapeutic agent 5-FU. In conclusion, this study shows that LMWPTP is not only overexpressed in colorectal cancer, but it is correlated with the malignant potential of this cancer, suggesting that this phosphatase may act as a predictive biomaker of CRC stage and represents a rational novel target in the treatment of this disease.
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影响因子：
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作者：
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作者：
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DOI：
10.1016/j.bbrc.2003.10.126
发表时间：
2003-12-12
影响因子：
3.1
作者：
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通讯作者：
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