Journal
CURRENT PHARMACEUTICAL DESIGN
Volume 20, Issue 39, Pages 6182-6190Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1381612820666140619123255
Keywords
Bone metastasis; EMT; highly metastatic tumors; less metastatic tumors; SPARC
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Funding
- Natural Science Foundation of China [31170890]
- 111 project [B06023]
- Fundamental Research Funds for the Central Universities [CDJXS112300]
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Cell migration and metastasis greatly contribute to the progression of tumors. Secreted Protein and Rich in Cysteine (SPARC), as a multi-faceted protein, is highly expressed in highly metastatic tumors while low or undetectable in less metastatic types with aberrant promoter methylation. In highly metastatic tumors, such as glioblastomas, melanoma, breast cancer and prostate cancer, SPARC promotes bone metastasis and epithelial-mesenchymal transition (EMT). In contrast, this protein acts as an anti-tumor factor in anti-angiogenesis, pro-apoptosis, cell proliferation inhibition and cell cycle arrest in less metastatic tumors, such as neuroblastoma, ovarian cancer, pancreatic cancer, colorectal cancer and gastric cancer. Here, we summarize and analyze the paradoxical role of SPARC in different tumors. We believe that further studies on truncated, alternative splicing variants and signal peptide of SPARC are required to elucidate the distinct effects. Most notably, SPARC variants probably play a crucial role in regulation of transforming growth factor beta (TGF-beta) induced EMT. This review also provides strategies to target or use SPARC (full-length, truncated and splicing variants) for therapeutic purposes.
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