We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
INTEGRA BIOSCIENCES AG

Download Mobile App




Novel Molecular Signaling Pathway Inhibits Lung Cancer Growth and Metastasis

By LabMedica International staff writers
Posted on 23 Nov 2015
Print article
A gene that had not been linked previously to lung cancer was found to be a critical component of a novel molecular signaling pathway that restricts lung cancer progression and metastasis.

Investigators at Northwestern University (Evanston, IL, USA) based the current study on emerging evidence that the neuronal guidance molecule SLIT played a role in tumor suppression, as SLIT-encoding genes were found to be inactivated in several types of cancer, including lung cancer. The SLIT gene produces the protein Slit, which in conjunction with the protein Robo (Roundabout) constitute a cell signaling pathway with many diverse functions including axon guidance and angiogenesis. Slit refers to a secreted protein which is most widely known as a repulsive axon guidance cue and Robo to its transmembrane protein receptor.

The investigators reported in the November 3, 2015, online edition of the Journal of Clinical Investigation that SLIT inhibited cancer cell migration by activating RhoA. RhoA (Ras homolog gene family, member A) is a small GTPase protein known to regulate the actin cytoskeleton in the formation of stress fibers. This protein is essential for the signaling function of the Rho GTPase complex.

The investigators found that myosin 9b (Myo9b) was a ROBO-interacting protein that suppressed RhoA activity in lung cancer cells. X-ray crystallography structural analyses revealed that the RhoGAP domain of Myo9b contained a unique patch that specifically recognized RhoA. The ROBO intracellular domain interacted with the Myo9b RhoGAP domain and inhibited its activity. Therefore, SLIT-dependent activation of RhoA was mediated by ROBO inhibition of Myo9b. In a mouse model, compared with control lung cancer cells, SLIT-expressing cells had a decreased capacity for tumor formation and lung metastasis.

In lung cancer cells, the intracellular domain (ICD) of ROBO directly interacted with the Myo9b RhoGAP domain and inhibited its activity. Thus, the negative regulation of Myo9b by SLIT/ROBO signaling in lung cancer cells activated RhoA and inhibited cell migration. Supporting this model, the data showed that SLIT inhibited lung tumor invasion and metastasis in a xenograft mouse model. Furthermore, Myo9b was highly expressed in human lung cancer tissues as compared with levels observed in the control samples. Consistently, increased Myo9b expression was associated with lymph node metastasis, advanced tumor stage, and poor patient survival.

These results implicate the existence of a previously unknown SLIT/ROBO/Myo9b/RhoA signaling pathway that inhibits cell migration and suppresses lung cancer metastasis.

“Elevated Myo9b expression is associated with fast lung cancer progression and poor prognosis,” said senior author Dr. Jane Wu, professor of neurology and psychiatry at Northwestern University. “These observations suggest the exciting possibility of developing Myo9b as a new biomarker for cancer, especially lung cancer. Our study provides new insights into the molecular and cellular mechanisms underlying lung cancer invasion and metastasis, a critical process that often leads to fatal consequence. Our data also provide a solid foundation for developing new diagnostic and therapeutic tools for lung cancer.”

Related Links:

Northwestern University


Platinum Member
COVID-19 Rapid Test
OSOM COVID-19 Antigen Rapid Test
Specimen Collection & Transport
Anti-Cyclic Citrullinated Peptide Test
GPP-100 Anti-CCP Kit
Gold Member
Real-time PCR System
GentierX3 Series

Print article

Channels

Clinical Chemistry

view channel
Image: Reaching speeds up to 6,000 RPM, this centrifuge forms the basis for a new type of inexpensive, POC biomedical test (Photo courtesy of Duke University)

POC Biomedical Test Spins Water Droplet Using Sound Waves for Cancer Detection

Exosomes, tiny cellular bioparticles carrying a specific set of proteins, lipids, and genetic materials, play a crucial role in cell communication and hold promise for non-invasive diagnostics.... Read more

Molecular Diagnostics

view channel
Image: The cobas Malaria test is the first FDA-approved molecular test to screen U.S. blood donors for malaria (Photo courtesy of Roche)

First FDA-Approved Molecular Test to Screen Blood Donors for Malaria Could Improve Patient Safety

Malaria, a serious illness that often leads to death, is spread by a specific mosquito species that infect humans with a parasite. Other transmission modes include blood transfusions, organ transplants,... Read more

Hematology

view channel
Image: The low-cost portable device rapidly identifies chemotherapy patients at risk of sepsis (Photo courtesy of 52North Health)

POC Finger-Prick Blood Test Determines Risk of Neutropenic Sepsis in Patients Undergoing Chemotherapy

Neutropenia, a decrease in neutrophils (a type of white blood cell crucial for fighting infections), is a frequent side effect of certain cancer treatments. This condition elevates the risk of infections,... Read more

Pathology

view channel
Image: The medical office procedure detects the key biomarker in Parkinson’s and related neurodegenerative diseases (Photo courtesy of BIDMC)

Simple Skin Biopsy Test Detects Parkinson’s and Related Neurodegenerative Diseases

Parkinson's disease and a group of related neurodegenerative disorders known as synucleinopathies impact millions globally. These conditions, including Parkinson’s disease (PD), dementia with Lewy bodies... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.