Talks
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Faculty
Presentation Type
Oral Presentation
Discipline Track
Community/Public Health
Abstract Type
Research/Clinical
Abstract
Background: Migration and Invasion Enhancer 1 (MIEN1) is a critical oncogene that drives cancer cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) in various cancers. MIEN1 overexpression is linked to aggressive tumor progression and poor prognosis. Despite its established role in cancer biology, targeted therapeutic options remain unexplored. This study aimed to identify and characterize first-in-class therapeutic molecules targeting the MIEN1 signaling pathway to inhibit cancer progression.
Methods: To develop novel bio-active peptides, we leveraged conserved immunoreceptor tyrosine-based activation motif (ITAM) and prenylation motifs within the MIEN1 protein sequence. Using rational peptide design, we identified and synthesized bioactive peptides, namely LA3IK and RP-7. RNA-seq analyses on untreated vs LA3IK and RP-7 treated MDA-MB-231 cells were conducted to check their effect on cancer progressing genes.
Functional assays were performed to assess the impact of the peptides on cancer cell migration and invasion. A scratch assay was conducted to evaluate the inhibition of cell migration, while Transwell invasion assays were used to quantify the suppression of invasive behavior. Scrambled peptide controls (LA3IK-SCR and RP-7-SCR) were utilized to confirm the specificity of the observed effects.
In vivo studies were conducted using an orthotopic breast cancer mouse model to assess the therapeutic efficacy of the peptides. Tumor growth inhibition was measured following peptide administration via intraperitoneal (30 mg/kg) routes. The Pharmacokinetic analyses were performed to evaluate peptide stability and bioavailability, with tolerability assessed at doses up to 90 mg/kg. Peptides were administered intravenously and intraperitoneally at varying doses to evaluate therapeutic efficacy and safety.
Results: Bioactive peptides LA3IK and RP-7 induced significant changes in gene and protein expression, inhibiting key drivers of cancer cell migration, invasion, and EMT at sub-IC50 concentrations. Both peptides suppressed EGF-induced NF-κB nuclear translocation in metastatic MDA-MB-231 breast cancer cells. Molecular studies confirmed the formation of MIEN1-peptide complexes, with the isoleucine residue in LA3IK and the CVIL motif in RP-7 being critical for activity. Scrambled peptides (LA3IK-SCR and RP-7-SCR) showed limited efficacy, highlighting specificity. In vivo, LA3IK and RP-7 significantly reduced tumor growth, with high tolerability at doses up to 90 mg/kg. Notably, D-isomers of the peptides demonstrated enhanced anti-cancer activity and superior pharmacokinetic properties. For example, D-LA3IK retained 75% stability in mouse plasma for 24 hours, surpassing D/L-RP-7 in pharmacokinetics and anti-cancer activity.
Conclusions: This study provides the first report of short peptides derived from the MIEN1 protein sequence as potent inhibitors of cancer signaling pathways. These peptides effectively suppressed tumor progression in vitro and in vivo, demonstrating promising therapeutic potential for targeting MIEN1-driven cancers. Their high specificity, stability, and tolerability highlight their translational potential as anti-cancer agents. Further studies are currently underway to investigate the role of these peptides in other cancer types.
Recommended Citation
Tripathi, Amit and Vishwanatha, Jamboor K., "First-in-class peptide molecules targeting the MIEN1 cancer signaling pathway, for which no inhibitors have been identified to date." (2025). Research Symposium. 3.
https://scholarworks.utrgv.edu/somrs/2025/talks/3
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Biochemistry Commons, Biotechnology Commons, Medicine and Health Sciences Commons, Molecular Biology Commons, Other Biochemistry, Biophysics, and Structural Biology Commons
First-in-class peptide molecules targeting the MIEN1 cancer signaling pathway, for which no inhibitors have been identified to date.
Background: Migration and Invasion Enhancer 1 (MIEN1) is a critical oncogene that drives cancer cell migration, invasion, and epithelial-to-mesenchymal transition (EMT) in various cancers. MIEN1 overexpression is linked to aggressive tumor progression and poor prognosis. Despite its established role in cancer biology, targeted therapeutic options remain unexplored. This study aimed to identify and characterize first-in-class therapeutic molecules targeting the MIEN1 signaling pathway to inhibit cancer progression.
Methods: To develop novel bio-active peptides, we leveraged conserved immunoreceptor tyrosine-based activation motif (ITAM) and prenylation motifs within the MIEN1 protein sequence. Using rational peptide design, we identified and synthesized bioactive peptides, namely LA3IK and RP-7. RNA-seq analyses on untreated vs LA3IK and RP-7 treated MDA-MB-231 cells were conducted to check their effect on cancer progressing genes.
Functional assays were performed to assess the impact of the peptides on cancer cell migration and invasion. A scratch assay was conducted to evaluate the inhibition of cell migration, while Transwell invasion assays were used to quantify the suppression of invasive behavior. Scrambled peptide controls (LA3IK-SCR and RP-7-SCR) were utilized to confirm the specificity of the observed effects.
In vivo studies were conducted using an orthotopic breast cancer mouse model to assess the therapeutic efficacy of the peptides. Tumor growth inhibition was measured following peptide administration via intraperitoneal (30 mg/kg) routes. The Pharmacokinetic analyses were performed to evaluate peptide stability and bioavailability, with tolerability assessed at doses up to 90 mg/kg. Peptides were administered intravenously and intraperitoneally at varying doses to evaluate therapeutic efficacy and safety.
Results: Bioactive peptides LA3IK and RP-7 induced significant changes in gene and protein expression, inhibiting key drivers of cancer cell migration, invasion, and EMT at sub-IC50 concentrations. Both peptides suppressed EGF-induced NF-κB nuclear translocation in metastatic MDA-MB-231 breast cancer cells. Molecular studies confirmed the formation of MIEN1-peptide complexes, with the isoleucine residue in LA3IK and the CVIL motif in RP-7 being critical for activity. Scrambled peptides (LA3IK-SCR and RP-7-SCR) showed limited efficacy, highlighting specificity. In vivo, LA3IK and RP-7 significantly reduced tumor growth, with high tolerability at doses up to 90 mg/kg. Notably, D-isomers of the peptides demonstrated enhanced anti-cancer activity and superior pharmacokinetic properties. For example, D-LA3IK retained 75% stability in mouse plasma for 24 hours, surpassing D/L-RP-7 in pharmacokinetics and anti-cancer activity.
Conclusions: This study provides the first report of short peptides derived from the MIEN1 protein sequence as potent inhibitors of cancer signaling pathways. These peptides effectively suppressed tumor progression in vitro and in vivo, demonstrating promising therapeutic potential for targeting MIEN1-driven cancers. Their high specificity, stability, and tolerability highlight their translational potential as anti-cancer agents. Further studies are currently underway to investigate the role of these peptides in other cancer types.
