# Role of SAP30 in hypoxia inducible factor activation and breast cancer progression

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $370,575

## Abstract

Tumor metastasis causes a high mortality of patients with triple-negative breast cancer (TNBC), but its underlying
mechanism remains unknown. Emerging studies showed that dysregulated gene transcription mediates TNBC
malignancy and tumor microenvironment is one of the critical regulators of gene dysregulation. Hypoxia-inducible
factors (HIFs), mainly HIF-1 and HIF-2, are the master transcriptional regulators in response to hypoxia, a
common feature of the tumor microenvironment, and activate their downstream target genes to regulate many
key processes in cancer biology, including angiogenesis, extracellular matrix remodeling, cell migration/invasion,
leading to TNBC progression and metastasis. Thus, understanding fundamental regulation of HIF transcriptional
activity would uncover the mechanism of TNBC progression and metastasis, which may lead to discovery of
therapeutic vulnerabilities in TNBC. To identify the novel regulator that controls HIF activity, we screened 720
epigenetic regulators and found that SAP30 is induced by HIF-1 and HIF-2, and in turn interacts with the alpha
subunit of HIF-1 and HIF-2 to enhances their target gene expression in TNBC cells. SAP30 is highly and
selectively expressed in human TNBC, and high levels of SAP30 are positively correlated with poor survival of
these patients. Genetic deletion of SAP30 blocks TNBC growth and lung metastasis in xenograft mice. These
exciting results suggest that SAP30 may act on HIFs-mediated gene dysregulation to promote TNBC progression
and metastasis. The central goal of the current R01 project is to dissect the detailed mechanisms by which
SAP30 increases HIF activation and TNBC progression and metastasis. Three Specific Aims are proposed to
address this goal. In Aim 1, we will define the underlying mechanism of SAP30 upregulation in TNBC by using
human TNBC cell lines and tissues. In Aim 2, we will decipher the regulatory mechanism of SAP30-mediated
HIF activation in TNBC. In Aim 3, we will dissect the molecular mechanisms of SAP30-dependent TNBC growth
and metastasis using SAP30 knockout mice we generated as well as human TNBC xenograft mice. The goal
will be achieved with great support from our outstanding collaborators on campus at UT Southwestern. The
successful completion of this project will provide new insights into the fundamental molecular mechanism
underlying TNBC progression and metastasis, and may uncover SAP30 as a therapeutic vulnerability in TNBC.

## Key facts

- **NIH application ID:** 9828087
- **Project number:** 5R01CA222393-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Weibo Luo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $370,575
- **Award type:** 5
- **Project period:** 2018-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9828087

## Citation

> US National Institutes of Health, RePORTER application 9828087, Role of SAP30 in hypoxia inducible factor activation and breast cancer progression (5R01CA222393-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9828087. Licensed CC0.

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