Protein phosphatase 1A (PPM1A) is involved in human cytotrophoblast cell invasion and migration |
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Authors: | Baohua Zhang Zhi Zhou Haiyan Lin Xiaoyin Lv Jiejun Fu Ping Lin Cheng Zhu Hongmei Wang |
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Institution: | (1) State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Chaoyang District, 100101 Beijing, China;(2) Graduate School of the Chinese Academy of Sciences, 100039 Beijing, China;(3) Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Harbin Medical University, 150081 Harbin, China |
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Abstract: | Trophoblast invasion is crucial for embryo implantation and placentation. Excessive trophoblast invasion leads to hydatidiform
moles and choriocarcinoma. PPM1A is a phosphatase which dephosphorylates and inactivates a broad range of substrates, including
TGF-β, MAP kinases, p38 and JNK kinase cascades, and is involved in tumor suppression. The objective of this study was to
investigate the expression of PPM1A in normal and malignant human placenta and its role in trophoblast invasion, which shares
many similarities with invasion of tumor cells. By Western blotting and immunocytochemistry, significantly higher expression
of PPM1A in human placental villi at term was found as compared with that during the first trimester. Furthermore, the expression
level of PPM1A protein in hydatidiform moles was lower compared with that during normal pregnancy. We further investigated
the function of PPM1A in extravillous trophoblast cell line HTR8/SVneo. Transwell migration and Matrigel invasion assays demonstrated
that PPM1A siRNA significantly promoted the motility and invasiveness of the cells. Gelatin zymography showed that knockdown
of PPM1A with siRNA elevated the expression of pro-matrix metalloproteinase pro-(MMP)-9, but down-regulated tissue inhibitors
of metalloproteinases (TIMP)-2. The present data indicate that PPM1A plays a critical role in the regulation of normal placentation
by inhibiting trophoblast migration and invasion. |
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Keywords: | PPM1A Hydatidiform moles Trophoblast invasion MMP TIMP |
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