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Crosstalk between critical cell-signaling pathways holds clues to tumor invasion and metastasis
Date:11/25/2009

HOUSTON - Two signaling pathways essential to normal human development - the Wnt/Wingless (Wnt) and epidermal growth factor receptor (EGFR) pathways - interact in ways that can promote tumor cell invasion and metastasis, researchers from The University of Texas M. D. Anderson Cancer Center report in the Nov. 25 issue of Molecular Cell.

This newly characterized interaction involves three signaling components known to correlate with invasive cancer - activation of EGFR, elevated protein kinase CK2 activity, and increased beta-catenin - T-cell factor/lymphoid enhancer factor (TCF/LEF-1) transcriptional activity.

"These findings highlight the importance of Wnt-independent and non-canonical activation of beta-catenin in tumor development," said senior author Zhimin Lu, MD, PhD, an associate professor in M. D. Anderson's Department of Neuro-Oncology. They also open up new possibilities for biomarkers that indicate prognosis or guide treatment.

Wnt Signaling and Cell-to-Cell Adhesion

Cell signaling is an intricate and precise process that enables cells to grow, differentiate (become specialized) and ultimately die (apoptosis). This orderly process is responsible for the normal development of organs and tissues. Alterations in the signaling within cells and between cells, however, can disrupt the cell-to-cell contact that helps keeps tumor cells in place. Loss of cell-to-cell contact leads to tumor cell migration, invasion and metastasis.

The Wnt signaling pathway plays a critical role in cell development, proliferation and differentiation. Mutations in this important pathway leading to the activation of beta-catenin are responsible for many types of cancer, including colon cancer. However, beta-catenin can also be activated in a mutation-independent manner in other cancers.

A key component of the Wnt pathway, beta-catenin combines with alpha-catenin and regulates cell-cell adhesion. It also interact
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

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