How cancer walk from one place to another?

Chunming Cheng, Xiangfei Kong, Hanzhou Wang, Huachen Gan, Yuqing Hao, Weiying Zou, Jingwen Wu, Yayun Chi, Junwu Yang, Yi Hong, Kangli Chen, Jianxin Gu

Overview

Metastasis is the main cause of death in patients with malignancy. We found that Trihydrophobin 1 (TH1) can inhibit PAK1 kinase activity and MAPK pathway, And, TH1 localized to feet of cancer cells (focal adhesions and filopodia in the leading edge of cells), where TH1 reduced cell migration through affecting actin and adhesion dynamics.

Summary

There are still many unresolved issues regarding how the signal of cell migration is regulated, when and where important molecular complexes form and disperse. We provided direct evidence that TH1 is a negative regulator of cancer growth and invasion.

Author Comments

Dr. Chunming Cheng, PhD
Dr. Chunming Cheng, PhD
The Ohio State University
Senior Research Associate
biochemistry
Columbus, OH | United States
It is one of my very interesting studies 10 years ago. I hope this article can inspire you besides providing insight into cancer. Dr. Chunming Cheng, PhD

Resources

original research article
http://dx.doi.org/10.1074/jbc.M806144200

Trihydrophobin 1 Interacts with PAK1 and Regulates ERK/MAPK Activation and Cell Migration.

Authors:
Dr. Chunming Cheng, PhD
Dr. Chunming Cheng, PhD
The Ohio State University
Senior Research Associate
biochemistry
Columbus, OH | United States

J Biol Chem 2009 Mar 9;284(13):8786-96. Epub 2009 Jan 9.

Gene Research Center, Shanghai Medical College, and Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

The Rac1/Cdc42 effector, p21-activated kinase (PAK), is activated by various signaling cascades, including receptor-tyrosine kinases and integrins, and regulates a number of processes such as cell proliferation and motility. PAK activity has been shown to be required for maximal activation of the canonical RAF-MEK-MAPK signaling cascade, possibly because of PAK co-activation of RAF and MEK. Here we have shown that trihydrophobin 1 (TH1), originally identified as a negative regulator of A-RAF kinase, also interacted with PAK1 in cultured cells. Confocal microscopy assay indicated that TH1 colocalized with PAK1 in both the cytoplasm and nucleus, which is consistent with our previous results. GST pulldown and coimmunoprecipitation experiments demonstrated that TH1 interacted directly with PAK1 and bound selectively to the carboxyl-terminal kinase domain of PAK1, and the ability of the binding was enhanced along with activation of PAK1. The binding pattern of PAK1 implies that this interaction was mediated in part by PAK1 kinase activity. As indicated by in vitro kinase activity assays and Western blot detections, TH1 inhibited PAK1 kinase activity and negatively regulated MAPK signal transduction. Interestingly, TH1 bound with MEK1/ERK in cells and in vitro without directly suppressing their kinase activity. Furthermore, we observed that TH1 localized to focal adhesions and filopodia in the leading edge of cells, where TH1 reduced cell migration through affecting actin and adhesion dynamics. Based on these observations, we propose a model in which TH1 interacts with PAK1 and specifically restricts the activation of MAPK modules through the upstream region of the MAPK pathway, thereby influencing cell migration.

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Source
http://dx.doi.org/10.1074/jbc.M806144200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2659237PMC
March 2009
93 Reads
6.140 Impact Factor

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