Heparanase Promotes Tumor Growth and Liver Metastasis of Colorectal Cancer Cells by Activating the p38/MMP1 Axis

Heparanase (HPSE), the only known mammalian endoglycosidase responsible for heparan sulfate cleavage, is a multi-faceted protein affecting multiple malignant behaviors in cancer cells. In this study, we examined the expression of HPSE in different colorectal cancer (CRC) cell lines. Gene manipulatio...

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Published inFrontiers in oncology Vol. 9; p. 216
Main Authors Liu, Xue, Zhou, Zhi-Hang, Li, Wen, Zhang, Shi-Kun, Li, Jing, Zhou, Ming-Ju, Song, Jin-Wen
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 02.04.2019
Subjects
colorectal cancer
extracellular matrix
heparanase
liver metastasis
MMP1
Oncology
liver metastasis
heparanase
colorectal cancer
MMP1
extracellular matrix
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Summary:Heparanase (HPSE), the only known mammalian endoglycosidase responsible for heparan sulfate cleavage, is a multi-faceted protein affecting multiple malignant behaviors in cancer cells. In this study, we examined the expression of HPSE in different colorectal cancer (CRC) cell lines. Gene manipulation was applied to reveal the effect of HPSE on proliferation, invasion, and metastasis of CRC. Knockdown of HPSE resulted in decreased cell proliferation , whereas overexpression of HPSE resulted in the opposite phenomenon. Consistently, data showed that knockdown of HPSE suppressed tumor growth of CRC. Furthermore, knockdown of HPSE inhibited invasion and liver metastasis and . RNA-sequencing analysis was performed upon knockdown of HPSE, and several pathways were identified that are closely associated with invasion and metastasis. In addition, HPSE is positively correlated with MMP1 expression in CRC, and HPSE regulates MMP1 expression via p38 MAPK signaling pathway. In conclusion, our data demonstrate that HPSE knockdown attenuated tumor growth and liver metastasis in CRC, implying that HPSE might serve as a potential therapeutic target in the treatment of CRC.
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Edited by: Giuliana Cassinelli, National Tumor Institute, Italy
This article was submitted to Cancer Molecular Targets and Therapeutics, a section of the journal Frontiers in Oncology
These authors have contributed equally to this work
Reviewed by: Maurizio Onisto, University of Padova, Italy; Jun Yan, Model Animal Research Center, Nanjing University, China
ISSN:2234-943X
2234-943X
DOI:10.3389/fonc.2019.00216