# Impact of N-Myc interactor on metastatic progression of breast cancer.

> **NIH VA I01** · BIRMINGHAM VA MEDICAL CENTER · 2020 · —

## Abstract

With increased participation of women in the military there is an increased need to effectively diagnose,
manage and cure breast cancer in the veteran population. The invasive and metastatic nature of this cancer
poses a formidable challenge. Our long term goal is to identify therapeutic avenues to effectively treat
metastasis of breast cancer. The objective of the proposed work is to understand the mechanistic and
functional consequences of the loss of a gatekeeper protein NMI, on breast cancer metastasis. We
hypothesize that loss of NMI unleashes unwarranted activation of Hh signaling and enhances the propensity
of breast cancer cells to metastasize. As our first Aim, we will employ thorough investigation using
innovative experimental approach to elucidate the mechanistic and functional consequences of NMI loss on
Hh driven metastatic progression of breast cancer. We will use a unique reagent created by us, to
determine whether the modulation of Hh signaling is via classical Hh ligand-dependent or non-classical Hh
ligand-independent mechanisms. We will characterize the molecular events that lead to activated Hh
signaling and interrogate the outcomes on cancer cell attributes of stemness, drug resistance and
mesenchymal phenotype. We also will employ in vivo assays that encompass xenograft studies and
investigations with genetically engineered mouse models that will enable us to specifically query activation
of Hh signaling in situations of NMI loss. In the second Aim, we will develop an understanding of the
correlative expression between NMI and molecular signatures of metastasis in tumor specimens derived
from Stage IV breast cancer patients. We will follow upon our findings that NMI expression is compromised
in hypoxic conditions, a finding with profound implications for metastasis; and test an innovative pre-clinical
pharmacological inhibition strategy to reduce metastasis of breast cancer that is devoid of NMI. Collectively,
this Aim will allow us to strengthen the clinical (translational) applicability of our observations and lay the
foundation to move towards a future clinical trial.

## Key facts

- **NIH application ID:** 9859313
- **Project number:** 5I01BX003374-04
- **Recipient organization:** BIRMINGHAM VA MEDICAL CENTER
- **Principal Investigator:** Rajeev S Samant
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-01-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859313

## Citation

> US National Institutes of Health, RePORTER application 9859313, Impact of N-Myc interactor on metastatic progression of breast cancer. (5I01BX003374-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9859313. Licensed CC0.

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