Journal
CANCER LETTERS
Volume 355, Issue 1, Pages 159-167Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2014.08.044
Keywords
Cyclin D1b; alpha v beta 3-integrin; HoxD3; Breast cancer; Invasion
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Funding
- National Science Foundation of China [81272314, 81171927]
- National Development Program (973) For Key Basic Research of China [2009CB521806]
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Cyclin D1b, a splice variant of the cell cycle regulator cyclin D1, holds oncogenic functions in human cancer. However, the mechanisms underlying cyclin D1b function remain poorly understood. Here we introduced wild-type cyclin D1a or cyclin D1b variant into non-metastatic MCF-7 cells. Our results show that ectopic expression of cyclin D1b promotes invasiveness of the cancer cells in a cyclin D1a independent manner. Specifically, cyclin D1b is found to modulate the expression of alpha v beta 3, which characterizes the metastatic phenotype, and enhance tumor cell invasive potential in cooperating with HoxD3. Notably, cyclin D1b promotes alpha v beta 3-mediated adhesion and invasive migration, which are associated with invasive potential of breast cancer cells. Further exploration indicates that cyclin D1b makes breast cancer cells more sensitive to toll-like receptor 4 ligand released from damaged tumor cells. These findings reveal a role of cyclin D1b as a possible mediator of alpha v beta 3 transcription to promote tumor metastasis. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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