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

s with alpha-catenin in the nucleus.

The alpha-catenin component of this beta-catenin/alpha-catenin complex has an inhibitory effect on beta-catenin that helps keep tumor cell migration and invasion in check. This inhibition is lost, however, when the EGFR pathway is activated. Upon activation, beta-catenin becomes untethered from alpha-catenin and translocates to the cell nucleus, where it increases expression of key target genes involved in tumor cell invasion and metastasis.

New Pathway Regulates Beta-Catenin Transactivation

The M. D. Anderson-led team made a surprising discovery: Beta-catenin also can travel to the nucleus via activation of the EGFR pathway-and it does so independently of Wnt signaling or mutations. The newly described pathway disrupts the beta-catenin/alpha catenin complex through an EGFR-extracellular receptor kinase (ERK)-protein kinase CK2- phosphorylation cascade. The investigators noted that this cascade culminates in the phosphorylation of alpha-catenin and ultimately promotes beta-catenin activation in the nucleus and subsequent tumor cell invasion.

The researchers found evidence of the newly identified pathway's clinical relevance when they examined human glioblastoma specimens. Specifically, levels of alpha-catenin phosphorylation correlated with levels of ERK activity and with grades of malignancy.

"Taken together, these findings demonstrate the importance of this pathway in tumor formation and progression," Dr. Lu said, "and they reveal potential markers for prognosis and therapeutics." Dr. Lu's lab is currently identifying genes downstream from beta-catenin that may be instrumental in tumor progression.

This research was supported by an American Cancer Society Research Scholar Award and grants from the Brain Tumor Society and Phi Beta Psi Sorority, an institutional research grant from M. D. Anderson Cancer Center; and a National Cancer Institute grant, all awarded to Lu. <
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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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Crosstalk between critical cell-signaling pathways holds clues to tumor invasion and metastasis
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