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A Novel Invadopodia-Specific Marker for Invasive and Pro-Metastatic Cancer Stem Cells

INTRODUCTION: Stem-like cancer cells or cancer stem cells (CSCs) may comprise a phenotypically and functionally heterogeneous subset of cells, whereas the molecular markers reflecting this CSC hierarchy remain elusive. The glycolytic enzyme alpha-enolase (ENO1) present on the surface of malignant tu...

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Autores principales: Huang, Shenq-Shyang, Liao, Wen-Ying, Hsu, Chung-Chi, Chan, Tze-Sian, Liao, Tai-Yan, Yang, Pei-Ming, Chen, Li-Tzong, Sung, Shian-Ying, Tsai, Kelvin K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200852/
https://www.ncbi.nlm.nih.gov/pubmed/34136381
http://dx.doi.org/10.3389/fonc.2021.638311
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author Huang, Shenq-Shyang
Liao, Wen-Ying
Hsu, Chung-Chi
Chan, Tze-Sian
Liao, Tai-Yan
Yang, Pei-Ming
Chen, Li-Tzong
Sung, Shian-Ying
Tsai, Kelvin K.
author_facet Huang, Shenq-Shyang
Liao, Wen-Ying
Hsu, Chung-Chi
Chan, Tze-Sian
Liao, Tai-Yan
Yang, Pei-Ming
Chen, Li-Tzong
Sung, Shian-Ying
Tsai, Kelvin K.
author_sort Huang, Shenq-Shyang
collection PubMed
description INTRODUCTION: Stem-like cancer cells or cancer stem cells (CSCs) may comprise a phenotypically and functionally heterogeneous subset of cells, whereas the molecular markers reflecting this CSC hierarchy remain elusive. The glycolytic enzyme alpha-enolase (ENO1) present on the surface of malignant tumor cells has been identified as a metastasis-promoting factor through its function of activating plasminogen. The expression pattern of surface ENO1 (sENO1) concerning cell-to-cell or CSC heterogeneity and its functional roles await further investigation. METHODS: The cell-to-cell expression heterogeneity of sENO1 was profiled in malignant cells from different types of cancers using flow cytometry. The subcellular localization of sENO1 and its functional roles in the invadopodia formation and cancer cell invasiveness were investigated using a series of imaging, molecular, and in vitro and in vivo functional studies. RESULTS: We showed here that ENO1 is specifically localized to the invadopodial surface of a significant subset (11.1%-63.9%) of CSCs in human gastric and prostate adenocarcinomas. sENO1(+) CSCs have stronger mesenchymal properties than their sENO1(-) counterparts. The subsequent functional studies confirmed the remarkable pro-invasive and pro-metastatic capacities of sENO1(+) CSCs. Mechanistically, inhibiting the surface localization of ENO1 by downregulating caveolin-1 expression compromised invadopodia biogenesis, proteolysis, and CSC invasiveness. CONCLUSIONS: Our study identified the specific expression of ENO1 on the invadopodial surface of a subset of highly invasive and pro-metastatic CSCs. sENO1 may provide a diagnostically and/or therapeutically exploitable target to improve the outcome of patients with aggressive and metastatic cancers.
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spelling pubmed-82008522021-06-15 A Novel Invadopodia-Specific Marker for Invasive and Pro-Metastatic Cancer Stem Cells Huang, Shenq-Shyang Liao, Wen-Ying Hsu, Chung-Chi Chan, Tze-Sian Liao, Tai-Yan Yang, Pei-Ming Chen, Li-Tzong Sung, Shian-Ying Tsai, Kelvin K. Front Oncol Oncology INTRODUCTION: Stem-like cancer cells or cancer stem cells (CSCs) may comprise a phenotypically and functionally heterogeneous subset of cells, whereas the molecular markers reflecting this CSC hierarchy remain elusive. The glycolytic enzyme alpha-enolase (ENO1) present on the surface of malignant tumor cells has been identified as a metastasis-promoting factor through its function of activating plasminogen. The expression pattern of surface ENO1 (sENO1) concerning cell-to-cell or CSC heterogeneity and its functional roles await further investigation. METHODS: The cell-to-cell expression heterogeneity of sENO1 was profiled in malignant cells from different types of cancers using flow cytometry. The subcellular localization of sENO1 and its functional roles in the invadopodia formation and cancer cell invasiveness were investigated using a series of imaging, molecular, and in vitro and in vivo functional studies. RESULTS: We showed here that ENO1 is specifically localized to the invadopodial surface of a significant subset (11.1%-63.9%) of CSCs in human gastric and prostate adenocarcinomas. sENO1(+) CSCs have stronger mesenchymal properties than their sENO1(-) counterparts. The subsequent functional studies confirmed the remarkable pro-invasive and pro-metastatic capacities of sENO1(+) CSCs. Mechanistically, inhibiting the surface localization of ENO1 by downregulating caveolin-1 expression compromised invadopodia biogenesis, proteolysis, and CSC invasiveness. CONCLUSIONS: Our study identified the specific expression of ENO1 on the invadopodial surface of a subset of highly invasive and pro-metastatic CSCs. sENO1 may provide a diagnostically and/or therapeutically exploitable target to improve the outcome of patients with aggressive and metastatic cancers. Frontiers Media S.A. 2021-05-31 /pmc/articles/PMC8200852/ /pubmed/34136381 http://dx.doi.org/10.3389/fonc.2021.638311 Text en Copyright © 2021 Huang, Liao, Hsu, Chan, Liao, Yang, Chen, Sung and Tsai https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Huang, Shenq-Shyang
Liao, Wen-Ying
Hsu, Chung-Chi
Chan, Tze-Sian
Liao, Tai-Yan
Yang, Pei-Ming
Chen, Li-Tzong
Sung, Shian-Ying
Tsai, Kelvin K.
A Novel Invadopodia-Specific Marker for Invasive and Pro-Metastatic Cancer Stem Cells
title A Novel Invadopodia-Specific Marker for Invasive and Pro-Metastatic Cancer Stem Cells
title_full A Novel Invadopodia-Specific Marker for Invasive and Pro-Metastatic Cancer Stem Cells
title_fullStr A Novel Invadopodia-Specific Marker for Invasive and Pro-Metastatic Cancer Stem Cells
title_full_unstemmed A Novel Invadopodia-Specific Marker for Invasive and Pro-Metastatic Cancer Stem Cells
title_short A Novel Invadopodia-Specific Marker for Invasive and Pro-Metastatic Cancer Stem Cells
title_sort novel invadopodia-specific marker for invasive and pro-metastatic cancer stem cells
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200852/
https://www.ncbi.nlm.nih.gov/pubmed/34136381
http://dx.doi.org/10.3389/fonc.2021.638311
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