Multi-layered proteogenomic analysis unravels cancer metastasis directed by MMP-2 and focal adhesion kinase signaling

Abstract The role of matrix metalloproteinase-2 (MMP-2) in tumor cell migration has been widely studied, however, the characteristics and effects of MMP-2 in clinical sample of metastatic colorectal cancer (CRC) remain poorly understood. Here, in order to unveil the perturbed proteomic signal during...

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Autores principales:	Yumi Kwon, Seong-Jun Park, Binh Thanh Nguyen, Mi Jeong Kim, Sejin Oh, Hwanho Lee, Narae Park, Hyun Seok Kim, Min-Jung Kang, Byung Soh Min, Jin-Won Lee, Eun Gyeong Yang, Cheolju Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/de6e57a07feb41a5899338b437cdc93b
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spelling	oai:doaj.org-article:de6e57a07feb41a5899338b437cdc93b2021-12-02T18:53:08ZMulti-layered proteogenomic analysis unravels cancer metastasis directed by MMP-2 and focal adhesion kinase signaling10.1038/s41598-021-96635-72045-2322https://doaj.org/article/de6e57a07feb41a5899338b437cdc93b2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96635-7https://doaj.org/toc/2045-2322Abstract The role of matrix metalloproteinase-2 (MMP-2) in tumor cell migration has been widely studied, however, the characteristics and effects of MMP-2 in clinical sample of metastatic colorectal cancer (CRC) remain poorly understood. Here, in order to unveil the perturbed proteomic signal during MMP-2 induced cancer progression, we analyzed plasma proteome of CRC patients according to disease progression, HCT116 cancer secretome upon MMP-2 knockdown, and publicly available CRC tissue proteome data. Collectively, the integrative analysis of multi-layered proteomes revealed that a protein cluster containing EMT (Epithelial-to-Mesenchymal Transition)-associated proteins such as CD9-integrin as well as MMP-2. The proteins of the cluster were regulated by MMP-2 perturbation and exhibited significantly increased expressions in tissue and plasma as disease progressed from TNM (Tumor, Node, and Metastasis) stage I to II. Furthermore, we also identified a plausible association between MMP-2 up-regulation and activation of focal adhesion kinase signaling in the proteogenomic analysis of CRC patient tissues. Based on these comparative and integrative analyses, we suggest that the high invasiveness in the metastatic CRC resulted from increased secretion of MMP-2 and CD9-integrin complex mediated by FAK signaling activation.Yumi KwonSeong-Jun ParkBinh Thanh NguyenMi Jeong KimSejin OhHwanho LeeNarae ParkHyun Seok KimMin-Jung KangByung Soh MinJin-Won LeeEun Gyeong YangCheolju LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yumi Kwon Seong-Jun Park Binh Thanh Nguyen Mi Jeong Kim Sejin Oh Hwanho Lee Narae Park Hyun Seok Kim Min-Jung Kang Byung Soh Min Jin-Won Lee Eun Gyeong Yang Cheolju Lee Multi-layered proteogenomic analysis unravels cancer metastasis directed by MMP-2 and focal adhesion kinase signaling
description	Abstract The role of matrix metalloproteinase-2 (MMP-2) in tumor cell migration has been widely studied, however, the characteristics and effects of MMP-2 in clinical sample of metastatic colorectal cancer (CRC) remain poorly understood. Here, in order to unveil the perturbed proteomic signal during MMP-2 induced cancer progression, we analyzed plasma proteome of CRC patients according to disease progression, HCT116 cancer secretome upon MMP-2 knockdown, and publicly available CRC tissue proteome data. Collectively, the integrative analysis of multi-layered proteomes revealed that a protein cluster containing EMT (Epithelial-to-Mesenchymal Transition)-associated proteins such as CD9-integrin as well as MMP-2. The proteins of the cluster were regulated by MMP-2 perturbation and exhibited significantly increased expressions in tissue and plasma as disease progressed from TNM (Tumor, Node, and Metastasis) stage I to II. Furthermore, we also identified a plausible association between MMP-2 up-regulation and activation of focal adhesion kinase signaling in the proteogenomic analysis of CRC patient tissues. Based on these comparative and integrative analyses, we suggest that the high invasiveness in the metastatic CRC resulted from increased secretion of MMP-2 and CD9-integrin complex mediated by FAK signaling activation.
format	article
author	Yumi Kwon Seong-Jun Park Binh Thanh Nguyen Mi Jeong Kim Sejin Oh Hwanho Lee Narae Park Hyun Seok Kim Min-Jung Kang Byung Soh Min Jin-Won Lee Eun Gyeong Yang Cheolju Lee
author_facet	Yumi Kwon Seong-Jun Park Binh Thanh Nguyen Mi Jeong Kim Sejin Oh Hwanho Lee Narae Park Hyun Seok Kim Min-Jung Kang Byung Soh Min Jin-Won Lee Eun Gyeong Yang Cheolju Lee
author_sort	Yumi Kwon
title	Multi-layered proteogenomic analysis unravels cancer metastasis directed by MMP-2 and focal adhesion kinase signaling
title_short	Multi-layered proteogenomic analysis unravels cancer metastasis directed by MMP-2 and focal adhesion kinase signaling
title_full	Multi-layered proteogenomic analysis unravels cancer metastasis directed by MMP-2 and focal adhesion kinase signaling
title_fullStr	Multi-layered proteogenomic analysis unravels cancer metastasis directed by MMP-2 and focal adhesion kinase signaling
title_full_unstemmed	Multi-layered proteogenomic analysis unravels cancer metastasis directed by MMP-2 and focal adhesion kinase signaling
title_sort	multi-layered proteogenomic analysis unravels cancer metastasis directed by mmp-2 and focal adhesion kinase signaling
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/de6e57a07feb41a5899338b437cdc93b
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Multi-layered proteogenomic analysis unravels cancer metastasis directed by MMP-2 and focal adhesion kinase signaling

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