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Original Article | Open Access

SHP-1 acts as a tumor suppressor by interacting with EGFR and predicts the prognosis of human breast cancer

Qian Geng1,2,*, Ruiting Xian1,*, Yinjue Yu1, Fengsheng Chen3, Rong Li1 ( )
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
Cancer Center, the Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 213003, China
Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China

*These authors contributed equally to this work.

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Abstract

Objective

The aims of this study were to examine the prognostic value of SHP-1 in breast cancer, its roles in the regulation of breast cancer cell growth and metastasis, and the underlying mechanisms.

Methods

Tumor specimens from 160 patients with breast cancer and 160 noncancerous tissues were used to examine the expression of SHP-1 and to analyze its association with overall survival through Kaplan–Meier and multivariate Cox regression analyses. RNA sequencing data and the expression and clinical importance of SHP-1 in breast cancer were evaluated with data from The Cancer Genome Atlas. In vitro and in vivo assays were performed to elucidate the effects of SHP-1 on breast cancer cell proliferation and invasion. Confocal immunofluorescence and GST pulldown assays were used to demonstrate the interaction between SHP-1 and epidermal growth factor receptor, as well as its downstream pathways. Immunohistochemistry and The Cancer Genome Atlas database were used to investigate the clinical association between SHP-1 and EGFR in human breast cancer.

Results

SHP-1 expression was associated with better survival in patients with breast cancer, whereas SHP-1 expression was negatively correlated with EGFR in human breast cancer. Ectopic SHP-1 expression significantly suppressed breast cancer cell proliferation, migration, and invasion. SHP-1 knockdown induced a more invasive phenotype and accelerated cell growth. Mechanistically, EGFR, a protein directly interacting with SHP-1, mediates the SHP-1-induced inactivation of Ras/Erk/GSK3β signaling and its downstream effectors.

Conclusions

SHP-1 is an important prognostic biomarker in patients with breast cancer, and the SHP-1-EGFR axis is a promising target for treatment.

Keywords

migrationbreast cancerproliferationEGFRSHP-1

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Cancer Biology & Medicine
Volume 19 Issue 4,
April 2022
Pages 468-485
DOI: 10.20892/j.issn.2095-3941.2020.0501
Cite this article:
Geng Q, Xian R, Yu Y, et al. SHP-1 acts as a tumor suppressor by interacting with EGFR and predicts the prognosis of human breast cancer. Cancer Biology & Medicine, 2022, 19(4): 468-485. https://doi.org/10.20892/j.issn.2095-3941.2020.0501

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Received: 28 August 2020
Accepted: 03 February 2021
Published: 01 April 2022
©2022 Cancer Biology & Medicine.

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