Jia Pei Lim, Sunitha Nair, Sukanya Shyamasundar, Pei Jou Chua, Umamaheswari Muniasamy, Ken Matsumoto, Jayantha Gunaratne, Boon Huat Bay, Silencing Y-box binding protein-1 inhibits triple-negative breast cancer cell invasiveness via regulation of MMP1 and beta-catenin expression, Cancer Letters, Volume 452, 2019, Pages 119-131, ISSN 0304-3835, https://doi.org/10.1016/j.canlet.2019.03.014.
Abstract:
Y-box binding protein-1 (YB-1), an important transcription and translation regulator protein, is known to increase cancer cell invasiveness and spreading. Here, we report its role in breast cancer, particularly in mediating cell invasion in triple-negative breast cancer (TNBC). YB-1 stable knockdown (shYB-1) significantly reduced the invasive potential of MDA-MB-231 TNBC cells in 2D and 3D (spheroid) cultures. Whole proteome mass spectrometry analysis showed an enrichment of cell adhesion and cell to matrix interaction proteins, notably, matrix metalloproteinase-1 (MMP1) and beta-catenin (CTNNB1), which are known to play critical roles in cancer metastasis. shYB-1 cells exhibited substantial downregulation of MMP1 and CTNNB1 mRNA and protein expression, with reduced MMP1 enzyme activity. YB-1 was also observed to bind to the promoter of MMP1 and overexpression of MMP1 plasmid in shYB-1 cells increased cell invasion. Finally, analysis of tumour samples from the Gene Expression-Based Outcome for Breast Cancer Online (GOBO) database revealed that high gene expressions of YBX1, MMP1 and CTNNB1 predict for a significantly lower 10-year distant metastasis free survival. Altogether, this study shows that YB-1 mediates breast cancer invasion and metastasis via regulation of MMP1 and beta-catenin.
License type:
http://creativecommons.org/licenses/by-nc-nd/4.0/
Funding Info:
We thank Ms Bay Song Lin for assistance in graphical illustration and Dr Cheng Teng Ng for technical assistance. Jia Pei Lim is a recipient of the Ong Hin Tiang Scholarship in Cancer Research. This research was supported by Ministry of Education Grant (MOE2013-T2-1-129).