An Oncogenic Protein Golgi Phosphoprotein 3 Up-regulates Cell Migration via Sialylation |
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| Authors: | Tomoya Isaji Sanghun Im Wei Gu Yuqin Wang Qinglei Hang Jishun Lu Tomohiko Fukuda Noritaka Hashii Daisuke Takakura Nana Kawasaki Hiroyuki Miyoshi Jianguo Gu |
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| Institution: | From the ‡Division of Regulatory Glycobiology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai, Miyagi 981-8558.;§National Institute of Health Sciences, Setagaya, Tokyo 158-0098, and ;¶RIKEN BioResource Center, Tsukuba, Ibaraki 305-0074, Japan |
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| Abstract: | Recently, the Golgi phosphoprotein 3 (GOLPH3) and its yeast homolog Vps74p have been characterized as essential for the Golgi localization of glycosyltransferase in yeast. GOLPH3 has been identified as a new oncogene that is commonly amplified in human cancers to modulate mammalian target of rapamycin signaling. However, the molecular mechanisms of the carcinogenic signaling pathway remain largely unclear. To investigate whether the expression of GOLPH3 was involved in the glycosylation processes in mammalian cells, and whether it affected cell behavior, we performed a loss-of-function study. Cell migration was suppressed in GOLPH3 knockdown (KD) cells, and the suppression was restored by a re-introduction of the GOLPH3 gene. HPLC and LC/MS analysis showed that the sialylation of N-glycans was specifically decreased in KD cells. The specific interaction between sialyltransferases and GOLPH3 was important for the sialylation. Furthermore, overexpression of α2,6-sialyltransferase-I rescued cell migration and cellular signaling, both of which were blocked in GOLPH3 knockdown cells. These results are the first direct demonstration of the role of GOLPH3 in N-glycosylation to regulate cell biological functions. |
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| Keywords: | Cell Migration Glycosylation Integrin Oncogene Sialyltransferase |
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