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- Title
Therapeutic Zfra4-10 or WWOX7-21 Peptide Induces Complex Formation of WWOX with Selective Protein Targets in Organs that Leads to Cancer Suppression and Spleen Cytotoxic Memory Z Cell Activation In Vivo.
- Authors
Su, Wan-Pei; Wang, Wan-Jen; Chang, Jean-Yun; Ho, Pei-Chuan; Liu, Tsung-Yun; Wen, Kuang-Yu; Kuo, Hsiang-Ling; Chen, Yu-Jie; Huang, Shenq-Shyang; Subhan, Dudekula; Chen, Yu-An; Lu, Chen-Yu; Wu, Chia-Yun; Lin, Sing-Ru; Lee, Ming-Hui; Chiang, Ming-Fu; Sze, Chun-I; Chang, Nan-Shan
- Abstract
Synthetic Zfra4-10 and WWOX7-21 peptides strongly suppress cancer growth in vivo. Hypothetically, Zfra4-10 binds to the membrane Hyal-2 of spleen Z cells and activates the Hyal-2/WWOX/SMAD4 signaling for cytotoxic Z cell activation to kill cancer cells. Stimulation of membrane WWOX in the signaling complex by a WWOX epitope peptide, WWOX7-21, is likely to activate the signaling. Here, mice receiving Zfra4-10 or WWOX7-21 peptide alone exhibited an increased binding of endogenous tumor suppressor WWOX with ERK, C1qBP, NF-κB, Iba1, p21, CD133, JNK1, COX2, Oct4, and GFAP in the spleen, brain, and/or lung which led to cancer suppression. However, when in combination, Zfra4-10 and WWOX7-21 reduced the binding of WWOX with target proteins and allowed tumor growth in vivo. In addition to Zfra4-10 and WWOX7-21 peptides, stimulating the membrane Hyal-2/WWOX complex with Hyal-2 antibody and sonicated hyaluronan (HAson) induced Z cell activation for killing cancer cells in vivo and in vitro. Mechanistically, Zfra4-10 binds to membrane Hyal-2, induces dephosphorylation of WWOX at pY33 and pY61, and drives Z cell activation for the anticancer response. Thus, Zfra4-10 and WWOX7-21 peptides, HAson, and the Hyal-2 antibody are of therapeutic potential for cancer suppression.
- Subjects
SPLEEN physiology; TUMOR suppressor genes; APOPTOSIS; CELL lines; CELLULAR signal transduction; HYALURONIC acid; LYMPHOCYTES; MEMBRANE proteins; PEPTIDES; PHOSPHORYLATION; PROTEINS; IN vivo studies
- Publication
Cancers, 2020, Vol 12, Issue 8, p2189
- ISSN
2072-6694
- Publication type
Article
- DOI
10.3390/cancers12082189