STEAP3 promotes cancer cell proliferation by facilitating nuclear trafficking of EGFR to enhance RAC1-ERK-STAT3 signaling in hepatocellular carcinoma

Abstract STEAP3 (Six-transmembrane epithelial antigen of the prostate 3, TSAP6, dudulin-2) has been reported to be involved in tumor progression in human malignancies. Nevertheless, how it participates in the progression of human cancers, especially HCC, is still unknown. In the present study, we fo...

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Autores principales:	Li-Li Wang, Jie Luo, Zhang-Hai He, Ye-Qing Liu, Hai-Gang Li, Dan Xie, Mu-Yan Cai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/c589815c01ed4aeab4e5d058b5272535
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spelling	oai:doaj.org-article:c589815c01ed4aeab4e5d058b52725352021-11-07T12:05:14ZSTEAP3 promotes cancer cell proliferation by facilitating nuclear trafficking of EGFR to enhance RAC1-ERK-STAT3 signaling in hepatocellular carcinoma10.1038/s41419-021-04329-92041-4889https://doaj.org/article/c589815c01ed4aeab4e5d058b52725352021-11-01T00:00:00Zhttps://doi.org/10.1038/s41419-021-04329-9https://doaj.org/toc/2041-4889Abstract STEAP3 (Six-transmembrane epithelial antigen of the prostate 3, TSAP6, dudulin-2) has been reported to be involved in tumor progression in human malignancies. Nevertheless, how it participates in the progression of human cancers, especially HCC, is still unknown. In the present study, we found that STEAP3 was aberrantly overexpressed in the nuclei of HCC cells. In a large cohort of clinical HCC tissues, high expression level of nuclear STEAP3 was positively associated with tumor differentiation and poor prognosis (p < 0.001), and it was an independent prognostic factor for HCC patients. In HCC cell lines, nuclear expression of STEAP3 significantly promoted HCC cells proliferation by promoting stemness phenotype and cell cycle progression via RAC1-ERK-STAT3 and RAC1-JNK-STAT6 signaling axes. Through upregulating the expression and nuclear trafficking of EGFR, STEAP3 participated in regulating EGFR-mediated STAT3 transactivity in a manner of positive feedback. In summary, our findings support that nuclear expression of STEAP3 plays a critical oncogenic role in the progression of HCC via modulation on EGFR and intracellular signaling, and it could be a candidate for prognostic marker and therapeutic target in HCC.Li-Li WangJie LuoZhang-Hai HeYe-Qing LiuHai-Gang LiDan XieMu-Yan CaiNature Publishing GrouparticleCytologyQH573-671ENCell Death and Disease, Vol 12, Iss 11, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Li-Li Wang Jie Luo Zhang-Hai He Ye-Qing Liu Hai-Gang Li Dan Xie Mu-Yan Cai STEAP3 promotes cancer cell proliferation by facilitating nuclear trafficking of EGFR to enhance RAC1-ERK-STAT3 signaling in hepatocellular carcinoma
description	Abstract STEAP3 (Six-transmembrane epithelial antigen of the prostate 3, TSAP6, dudulin-2) has been reported to be involved in tumor progression in human malignancies. Nevertheless, how it participates in the progression of human cancers, especially HCC, is still unknown. In the present study, we found that STEAP3 was aberrantly overexpressed in the nuclei of HCC cells. In a large cohort of clinical HCC tissues, high expression level of nuclear STEAP3 was positively associated with tumor differentiation and poor prognosis (p < 0.001), and it was an independent prognostic factor for HCC patients. In HCC cell lines, nuclear expression of STEAP3 significantly promoted HCC cells proliferation by promoting stemness phenotype and cell cycle progression via RAC1-ERK-STAT3 and RAC1-JNK-STAT6 signaling axes. Through upregulating the expression and nuclear trafficking of EGFR, STEAP3 participated in regulating EGFR-mediated STAT3 transactivity in a manner of positive feedback. In summary, our findings support that nuclear expression of STEAP3 plays a critical oncogenic role in the progression of HCC via modulation on EGFR and intracellular signaling, and it could be a candidate for prognostic marker and therapeutic target in HCC.
format	article
author	Li-Li Wang Jie Luo Zhang-Hai He Ye-Qing Liu Hai-Gang Li Dan Xie Mu-Yan Cai
author_facet	Li-Li Wang Jie Luo Zhang-Hai He Ye-Qing Liu Hai-Gang Li Dan Xie Mu-Yan Cai
author_sort	Li-Li Wang
title	STEAP3 promotes cancer cell proliferation by facilitating nuclear trafficking of EGFR to enhance RAC1-ERK-STAT3 signaling in hepatocellular carcinoma
title_short	STEAP3 promotes cancer cell proliferation by facilitating nuclear trafficking of EGFR to enhance RAC1-ERK-STAT3 signaling in hepatocellular carcinoma
title_full	STEAP3 promotes cancer cell proliferation by facilitating nuclear trafficking of EGFR to enhance RAC1-ERK-STAT3 signaling in hepatocellular carcinoma
title_fullStr	STEAP3 promotes cancer cell proliferation by facilitating nuclear trafficking of EGFR to enhance RAC1-ERK-STAT3 signaling in hepatocellular carcinoma
title_full_unstemmed	STEAP3 promotes cancer cell proliferation by facilitating nuclear trafficking of EGFR to enhance RAC1-ERK-STAT3 signaling in hepatocellular carcinoma
title_sort	steap3 promotes cancer cell proliferation by facilitating nuclear trafficking of egfr to enhance rac1-erk-stat3 signaling in hepatocellular carcinoma
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/c589815c01ed4aeab4e5d058b5272535
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STEAP3 promotes cancer cell proliferation by facilitating nuclear trafficking of EGFR to enhance RAC1-ERK-STAT3 signaling in hepatocellular carcinoma

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