Tzu Chi Medical Journal

REVIEW ARTICLE
Year
: 2021  |  Volume : 33  |  Issue : 4  |  Page : 332--338

Regulation on tumor metastasis by Raf kinase inhibitory protein: New insight with reactive oxygen species signaling


Chi-Tan Hu1, Jaya Prakash Mandal2, Wen-Sheng Wu3 
1 Division of Gastroenterology, Department of Medicine; Research Centre for Hepatology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; School of Medicine, Tzu Chi University, Hualien, Taiwan
2 Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
3 Institute of Medical Sciences, Tzu Chi University; Division of General Surgery, Department of Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; Department of Laboratory Medicine and Biotechnology, College of Medicine, Tzu Chi University, Hualien, Taiwan

Correspondence Address:
Wen-Sheng Wu
Division of General Surgery, Department of Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 707, Section 3, Chung-Yang Road, Hualien
Taiwan

Targeted therapy aiming at the metastatic signal pathway, such as that triggered by receptor tyrosine kinase (RTK), for the prevention of tumor progression is promising. However, RTK-based targeted therapy frequently suffered from drug resistance due to the co-expression of multiple growth factor receptors that may raise compensatory secondary signaling and acquired mutations after treatment. One alternative strategy is to manipulate the common negative regulators of the RTK signaling. Among them, Raf kinase inhibitory protein (RKIP) is highlighted and focused on this review. RKIP can associate with Raf-1, thus suppressing the downstream mitogen-activated protein kinase (MAPK) cascade. RKIP also negatively regulates other metastatic signal molecules including NF-κB, STAT3, and NOTCH1. In general, RKIP achieves this task via associating and blocking the activity of the critical molecules on upstream of the aforementioned pathways. One novel RKIP-related signaling involves reactive oxygen species (ROS). In our recent report, we found that PKCδ-mediated ROS generation may interfere with the association of RKIP with heat shock protein 60 (HSP60)/MAPK complex via oxidation of HSP60 triggered by the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate. The departure of RKIP may impact the downstream MAPK in two aspects. One is to trigger the Mt→cytosol translocation of HSP60 coupled with MAPKs. The other is to change the conformation of HSP60, favoring more efficient activation of the associated MAPK by upstream kinases in cytosol. It is worthy of investigating whether various RTKs capable of generating ROS can drive metastatic signaling via affecting RKIP in the same manner.


How to cite this article:
Hu CT, Mandal JP, Wu WS. Regulation on tumor metastasis by Raf kinase inhibitory protein: New insight with reactive oxygen species signaling.Tzu Chi Med J 2021;33:332-338


How to cite this URL:
Hu CT, Mandal JP, Wu WS. Regulation on tumor metastasis by Raf kinase inhibitory protein: New insight with reactive oxygen species signaling. Tzu Chi Med J [serial online] 2021 [cited 2021 Dec 1 ];33:332-338
Available from: https://www.tcmjmed.com/article.asp?issn=1016-3190;year=2021;volume=33;issue=4;spage=332;epage=338;aulast=Hu;type=0