Title:Isoproterenol-induced Upregulation of HPSE Accelerates Triple-negative Breast
Cancer Cell Proliferation and Migration through Enhancing the Transcriptional Activity
of HIF-1α
Volume: 23
Issue: 4
Author(s): Jian Qiu, Zhongyi Shen, Guoqin Jiang*Qichao Ni*
Affiliation:
- Thyroid and Breast Surgery, The
Second Affiliated Hospital of Soochow University, Suzhou, 215004, Jiangsu, China
- Thyroid and Breast Surgery, Affiliated Hospital
of Nantong University, Nantong, 226001, Jiangsu, China
Keywords:
HPSE, isoproterenol, HIF1A, triple-negative breast cancer, upregulation, transcriptional activity.
Abstract:
Background: Triple-negative breast cancer (TNBC) is considered to be the most malignant subtype of
breast cancer (BC). Heparanase (HPSE) has been reported to contribute to tumor development, but its potential function
in TNBC is not clear. The intention of this study was to investigate whether HPSE affects TNBC progression and
to explore the possible mechanisms.
Methods: Bioinformatics analyses were applied to analyze the expression of HPSE in TNBC samples and normal
breast samples. The mRNA and protein levels of HPSE in TNBC cells were detected by RT-qPCR and western blot.
Function assays, including CCK-8 assay, colony formation assay, transwell assay and wound healing assay, were conducted
to validate the effects of HPSE silencing on TNBC cell proliferation and migration. Mechanism experiments
were performed to explore the upstream molecular mechanism of HPSE in TNBC cells.
Results: Silencing of HPSE suppressed the proliferation and migration of TNBC cells. Moreover, hypoxia-inducible
factor-1 alpha (HIF-1α) interacted with the HPSE promoter and promoted the transcription of HPSE. Isoproterenol
(ISO), a pharmacological substitute for chronic stress-induced sympathetic activation, was proven to induce HIF-1α
upregulation, so as to transcriptionally activate HPSE in TNBC cells. Furthermore, it manifested that ISO facilitated
TNBC cell proliferation and migration in an HPSE-dependent way.
Conclusion: HPSE activated by ISO-induced HIF-1α promoted TNBC cell proliferation and migration, which might
offer a novel insight for TNBC treatment.
