Navigation Links
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 interacts 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.


'/>"/>

Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

Related medicine news :

1. Angioplasty Outcomes May Vary Little Between Hospitals
2. Experts Examine Possible Links Between Climate Change and Infectious Disease Transmission
3. American College of Cardiology/American Heart Association Comment on the FDA Public Health Advisory Regarding a Drug Interaction Between Clopidogrel and Omeprazole
4. K-State researchers studying link between climate change and cattle nutritional stress
5. Connection between depression and osteoporosis detailed by Hebrew University researchers
6. Researchers discover links between city walkability and air pollution exposure
7. Intervals between lung cancer diagnosis and treatment displays a health care disparity
8. Study reveals possible link between IBD therapy and skin cancer
9. New studies explore connection between high stress jobs and GI disorders
10. Pitt study shows linkage between teen girls weight and sexual behavior
11. Gastroenterologists explore relationship between bacteria in the gut and breast cancer
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Crosstalk between critical cell-signaling pathways holds clues to tumor invasion and metastasis
(Date:1/17/2017)... ... , ... January is National Stalking Awareness Month (NSAM), now in its fourteenth year, ... commit the crime of stalking, a very real danger to many in our community. ... stalking and other crimes. , “Stalking: know it. Name it. Stop it.”—so reads the theme ...
(Date:1/17/2017)... ... 17, 2017 , ... For breast cancer clinicians and researchers who were unable ... a more intimate review and analysis of its highlights, a novel half-day, complimentary meeting—the ... by Imedex on February 4, 2017 in Chicago. Chaired by Kathy S. Albain, MD, ...
(Date:1/17/2017)... ... January 17, 2017 , ... Kevin Harrington (one of the original ... featuring DRTV campaigns regarding the topic of Beauty and Personal Care. ... themselves. What better way to commit to these changes than beginning with personal care ...
(Date:1/17/2017)... ... January 17, 2017 , ... Mirror Mirror Beauty Boutique, Houston’s premiere CoolSculpting ... Level in Zeltiq’s Crystal Rewards Program. Practice founder, Paul Vitenas, MD FACS, is delighted ... providers. , Produced by Zeltiq, CoolSculpting is approved by the Food and Drug ...
(Date:1/17/2017)... ... 17, 2017 , ... A prescription medication bottle, pocket knife, luggage and a ... Cradle Product Design Challenge , the Cradle to Cradle Products Innovation Institute ... challenges scheduled to run through early 2018. The challenges are presented by the Institute ...
Breaking Medicine News(10 mins):
(Date:1/17/2017)... 2017 Precision medicine is an emerging ... of disease. The approach allows doctors and physicians ... The approach studies the individual profile at a ... In January 2015, Precision Medicine Initiative (PMI) was ... with more than one million volunteers. All of ...
(Date:1/17/2017)... Pa. , Jan. 17, 2017 Secretary ... and Alcohol Programs Secretary Gary Tennis are ... carfentanil, following two recent overdose deaths from the drug ... "Carfentanil is intended to sedate large animals and ... kill anyone who comes into contact with it," Secretary ...
(Date:1/17/2017)... YORK , Jan. 17, 2017 EU5 ... GlobalData,s new report, "EU5 Glucose Monitoring Market Outlook ... Glucose Monitoring market. The report provides value, in millions ... (USD) within market segments - Blood Glucose Meters, Blood ... provides company shares and distribution shares data for each ...
Breaking Medicine Technology: