# ErbB3-miRNA axis in tumor metastasis of erbB2-positive breast cancer > **NIH NIH R01** · LSU HEALTH SCIENCES CENTER · 2020 · $336,263 ## Abstract Elevated expression of erbB3 receptor correlates with increased distant metastasis of breast cancers with amplification and/or overexpression of erbB2 (HER2/neu), which occur in approximately 25-30% of invasive breast cancers and are significantly associated with a worse prognosis in breast cancer patients. The erbB3 receptor frequently co-expresses and interacts with erbB2 in breast cancer to activate the oncogenic signaling, especially the PI-3K/Akt pathway and Src kinase. ErbB3 serves as a co-receptor of erbB2 and plays a critical role in the development of erbB2-overexpressing (erbB2+) breast cancer. Our recent data reveal that overexpression of erbB3 decreases, and inhibition of erbB3 signaling with an erbB3 specific shRNA, an anti-erbB3 blocking antibody (Ab), or an Akt inhibitor increases the levels of miR-203 and miR- 542-3p in erbB2+ breast cancer cells. Interestingly, both miR-203 and miR-542-3p have been identified as tumor suppressive miRNAs, and are frequently downregulated due to promoter methylation in various human cancers, including breast cancer. Bioinformatics analysis suggests that miR-203 and/or miR-542-3p target several critical genes, including Survivin, ZEB1, ZEB2, Snail1, and/or Slug, responsible for drug resistance, epithelial-mesenchymal transition (EMT), and tumor metastasis. We also discover an enhanced expression of ZEB1, Snail1, Slug, and Vimentin upon ectopic expression of erbB3 in erbB2+ breast cancer cells. Thus, we hypothesize that activation of erbB3 signaling promotes erbB2+ breast cancer metastasis via epigenetic silencing of the tumor suppressive miR-203/miR-542-3p and effective inhibition of erbB3 will significantly suppress metastasis via induction of miR-203/miR-542-3p. We intend to define miR- 203 and miR-542-3p as the key downstream mediators of erbB3 signaling to enhance metastatic potential of erbB2+ breast cancer cells by upregulating the EMT markers; and identify novel strategy/agents inhibiting erbB3 to prevent or attenuate erbB2+ breast cancer metastasis via induction of miR-203/miR-542-3p. ## Key facts - **NIH application ID:** 9763330 - **Project number:** 5R01CA201011-05 - **Recipient organization:** LSU HEALTH SCIENCES CENTER - **Principal Investigator:** Bolin Liu - **Activity code:** R01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $336,263 - **Award type:** 5 - **Project period:** 2016-09-01 → 2022-08-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/9763330 ## Citation > US National Institutes of Health, RePORTER application 9763330, ErbB3-miRNA axis in tumor metastasis of erbB2-positive breast cancer (5R01CA201011-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9763330. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*