HYAL-2-WWOX-SMAD4 Signaling in Cell Death and Anticancer Response

Hyaluronidase HYAL-2 is a membrane-anchored protein and also localizes, in part, in the lysosome. Recent study from animal models revealed that both HYAL-1 and HYAL-2 are essential for the metabolism of hyaluronan (HA). deficiency is associated with chronic thrombotic microangiopathy with hemolytic...

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Published in:Frontiers in cell and developmental biology 2016-12, Vol.4, p.141-141
Main Authors: Hsu, Li-Jin, Chiang, Ming-Fu, Sze, Chun-I, Su, Wan-Pei, Yap, Ye Vone, Lee, I-Ting, Kuo, Hsiang-Ling, Chang, Nan-Shan
Format: Article
Language:English
Subjects:
Cancer
Cell and Developmental Biology
Hyaluronidase
Peptides
Polymerization
prevention
Treatment
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Summary:Hyaluronidase HYAL-2 is a membrane-anchored protein and also localizes, in part, in the lysosome. Recent study from animal models revealed that both HYAL-1 and HYAL-2 are essential for the metabolism of hyaluronan (HA). deficiency is associated with chronic thrombotic microangiopathy with hemolytic anemia in mice due to over accumulation of high molecular size HA. HYAL-2 is essential for platelet generation. Membrane HYAL-2 degrades HA bound by co-receptor CD44. Also, in a non-canonical signal pathway, HYAL-2 serves as a receptor for transforming growth factor beta (TGF-β) to signal with downstream tumor suppressors WWOX and SMAD4 to control gene transcription. When SMAD4 responsive element is overly driven by the HYAL-2-WWOX-SMAD4 signaling complex, cell death occurs. When rats are subjected to traumatic brain injury, over accumulation of a HYAL-2-WWOX complex occurs in the nucleus to cause neuronal death. HA induces the signaling of HYAL-2-WWOX-SMAD4 and relocation of the signaling complex to the nucleus. If the signaling complex is overexpressed, bubbling cell death occurs in WWOX-expressing cells. In addition, a small synthetic peptide Zfra (zinc finger-like protein that regulates apoptosis) binds membrane HYAL-2 of non-T/non-B spleen HYAL-2 CD3 CD19 Z lymphocytes and activates the cells to generate memory anticancer response against many types of cancer cells . Whether the HYAL-2-WWOX-SMAD4 signaling complex is involved is discussed. In this review and opinion article, we have updated the current knowledge of HA, HYAL-2 and WWOX, HYAL-2-WWOX-SMAD4 signaling, bubbling cell death, and Z cell activation for memory anticancer response.
ISSN:2296-634X
2296-634X
DOI:10.3389/fcell.2016.00141