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Ansari et al. J Cancer Metastasis Treat 2019;5:20 Journal of Cancer
DOI: 10.20517/2394-4722.2018.68 Metastasis and Treatment

Original Article Open Access

Synergistic inhibition of SCR1- and ERBB2-driven
brain metastatic breast cancer cells

Shahnaz R. Ansari , Zain Jandial , Xiwei Wu , Xueli Liu , Mike Y. Chen , Khairul I. Ansari 1
3
2
1
1
1
1 Division of Neurosurgery, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
2 Department of Molecular and Cellular Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
3 Division of Biostatistics, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.
Correspondence to: Dr. Khairul I. Ansari, Division of Neurosurgery, Beckman Research Institute, City of Hope, Duarte, CA 91010,
USA. E-mail: kansari@coh.org
How to cite this article: Ansari SR, Jandial Z, Wu X, Liu X, Chen MY, Ansari KI. Synergistic inhibition of SCR1- and ERBB2-driven
brain metastatic breast cancer cells. J Cancer Metastasis Treat 2019;5:20. http://dx.doi.org/10.20517/2394-4722.2018.68
Received: 24 Oct 2018 First Decision: 14 Jan 2019 Revised: 18 Jan 2019 Accepted: 6 Feb 2019 Published: 22 Mar 2019

Science Editor: William P. Schiemann Copy Editor: Cai-Hong Wang Production Editor: Huan-Liang Wu

Abstract
Aim: Metastasis to the brain has become a major limitation to the life expectancy and quality of life for many patients
with breast cancer. Unfortunately, other than radiation and palliative treatments with trastuzumab, and pertuzumab,
no effective therapy for brain metastases is currently available. This study seeks to identify novel gene targets and
pharmaceutical Intervention against breast cancer brain metastasis.

Methods: The detailed methods applied to this study, including comparative RNA sequencing and bioinformatics
analysis of sequence data, ingenuity pathway analysis, protein-protein interaction analysis, high throughput screening
of clinical and pre-clinical drugs, cell viability and proliferation assay, toxicity and apoptosis assay using fluorescence-
activated cell sorting, real-time PCR, western blotting, statistical analysis of data.

Results: The study reveals critical roles for SRC, ERBB2, PIK3CA, and GABA in the proliferation and survival of breast
cancer brain metastatic (BBM) cells and showed that SRC- and ERBB2-mediated activation of PIK3-AKT/mTOR
signaling regulates BBM cell survival. Selective inhibition of these candidate genes alone or in combination induces
robust apoptosis in BBM cells

Conclusion: The findings of this study provide a rationale for further preclinical evaluation of SRC-targeting regimens
in combination with ERBB2 inhibitors and/or GABA agonists to target breast cancer brain metastasis.

Keywords: Breast cancer, brain metastasis, human epidermal growth factor receptor 2, ERBB2, SRC, astrocytes,
PI3KCA

© The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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