Details

Autor(en) / Beteiligte

• Zhu, X.H.
• Wang, J.M.
• Yang, S.S.
• Wang, F.F.
• Hu, J.L.
• Xin, S.N.
• Men, H.
• Lu, G.F.
• Lan, X.L.
• Zhang, D.
• Wang, X.Y.
• Liao, W.T.
• Ding, Y.Q.
• Liang, L.

Titel

Down‐regulation of DAB2IP promotes colorectal cancer invasion and metastasis by translocating hnRNPK into nucleus to enhance the transcription of MMP2

Ist Teil von

• International journal of cancer, 2017-07, Vol.141 (1), p.172-183

Ort / Verlag

United States: Wiley Subscription Services, Inc

Erscheinungsjahr

2017

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• DOC‐2/DAB2 interacting protein (DAB2IP) is a RasGAP protein that shows a suppressive effect on cancer progression. Our previous study showed the involvement of transcription regulation of DAB2IP in metastasis of colorectal cancer (CRC). However, the molecular mechanisms of DAB2IP in regulating the progression of CRC need to be further explored. Here, we identified heterogeneous nuclear ribonucleoprotein K (hnRNPK) and matrix metalloproteinase 2 (MMP2) as vital downstream targets of DAB2IP in CRC cells by two‐dimensional fluorescence difference gel electrophoresis and cDNA microassay, respectively. Mechanistically, down‐regulation of DAB2IP increased the level of hnRNPK through MAPK/ERK signaling pathway. Subsequently, translocation of hnRNPK into nucleus enhanced the transcription activity of MMP2, and therefore promoted invasion and metastasis of CRC. Down‐regulation of DAB2IP correlated negatively with hnRNPK and MMP2 expressions in CRC tissues. In conclusion, our study elucidates a novel mechanism of the DAB2IP/hnRNPK/MMP2 axis in the regulation of CRC invasion and metastasis, which may be a potential therapeutic target. What's new? DAB2IP is a RasGAP protein that suppresses cancer progression. It is also involved in metastasis of colorectal cancer (CRC). However, the molecular mechanisms are not well understood. In this study, the authors identified several downstream proteins that are regulated by DAB2IP in CRC cells, and revealed how down‐regulation of DAB2IP alters transcription in CRC. These results provide a novel mechanism for the role of DAB2IP/hnRNPK/MMP2 axis in the regulation of CRC invasion and metastasis, which may, in turn, offer a potential therapeutic target.