New publication: Tiny peptide may help block aggressive prostate cancer signaling
A peptide made of just six amino acids may offer a new way to slow the spread of aggressive prostate cancer, according to researchers at UNT Health Fort Worth.
In a study published last month in Scientific Reports, scientists led by Amit K. Tripathi, Nafees Ahamad, Pragati Singh, and senior investigator Jamboor K. Vishwanatha report that a short peptide called LA3IK can disrupt a key molecular interaction that helps prostate cancer cells become more aggressive.
Many prostate tumors rely on signals from the Epidermal Growth Factor Receptor (EGFR), a protein on the surface of cells that responds to growth signals. In advanced cancers, EGFR often partners with another receptor, ERBB2, forming a pair that activates powerful pathways that drive tumor invasion, migration, and the formation of new blood vessels.
“This work was inspired by our interest in understanding how prostate cancer cells use growth factor signaling to become more aggressive. In many advanced tumors, signals from EGFR help cancer cells migrate, invade surrounding tissues, and promote angiogenesis,” said Dr. Amit K. Tripathi, research assistant professor at the College of Biomedical and Translational Sciences and lead author of the study.
“We wanted to explore whether a small, targeted peptide could disrupt these specific signaling events without broadly shutting down normal cellular functions. That idea led us to develop and study LA3IK, a short peptide derived from MIEN1 that can interfere with EGFR–ERBB2 interaction.”
The research team found that the peptide LA3IK interferes with this pairing. By disrupting EGFR–ERBB2 heterodimerization, the peptide reduced phosphorylation of EGFR and suppressed several cancer-promoting signaling pathways involving NF-κB, Src, and STAT3.
Experiments performed in PC3 prostate cancer cells, a model of advanced prostate cancer, showed that the peptide significantly reduced cancer cell migration and invasion. Further transcriptomic analyses revealed decreased expression of angiogenesis-related genes such as ANGPTL4 and VEGFC, which are associated with tumor blood vessel formation.
Importantly, the researchers observed that LA3IK suppressed EGF signaling in prostate tumors while preserving normal EGFR function in healthy liver tissue. This selective activity suggests that the peptide may have fewer side effects than treatments that broadly block growth factor signaling.
The team reports that LA3IK is the shortest peptide identified so far that can effectively inhibit EGF-driven tumorigenic signaling, highlighting its potential as a new precision approach for targeting advanced prostate cancer.
“Seeing this work published is very meaningful to me because it represents years of collaborative effort, persistence, and curiosity. Research often involves many challenges and unexpected results, so reaching this point feels both rewarding and motivating to continue exploring new therapeutic strategies,” Tripathi said.
“CBTS has played an important role in this journey. The collaborative environment, access to resources, and guidance from mentors allowed us to test new ideas and carry out the multidisciplinary experiments needed for this project. Being part of CBTS provided the support and scientific community that helped move this research forward.”
You can read the full study here: An MIEN1-based hexamer peptide (LA3IK) inhibits EGF-driven oncogenic signaling in prostate cancer by disrupting EGFR–ERBB2 heterodimerization