MicroRNA-375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma

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Abstract

Context.-Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an association with locoregional recurrence and lymph node metastasis. We have previously reported that low microRNA-375 (miR-375) expression levels correlate with poor patient survival, increased locoregional recurrence, and distant metastasis. Increasing miR-375 expression in HNSCC cell lines to levels found in normal cells results in suppressed invasive properties. HNSCC invasion is mediated in part by invadopodia-associated degradation of the extracellular matrix. Objective.-To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. Design.-For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of cortactin. Human protease arrays were used for the detection of the secreted proteases. Quantitative real time-polymerase chain reaction measurements were used to evaluate the messenger RNA (mRNA) expression of the commonly regulated proteases. Results.-Increased miR-375 expression in HNSCC cells suppresses extracellular matrix degradation and reduces the number of mature invadopodia. Higher miR-375 expression does not reduce cellular levels of selected invadopodia-associated proteins, nor is tyrosine phosphorylation of cortactin altered. However, HNSCC cells with higher miR-375 expression had significant reductions in the mRNA expression levels and secreted levels of specific proteases. Conclusions.-MicroRNA-375 regulates invadopodia maturation and function potentially by suppressing the expression and secretion of proteases.

Original languageEnglish (US)
Pages (from-to)1349-1361
Number of pages13
JournalArchives of Pathology and Laboratory Medicine
Volume139
Issue number11
DOIs
StatePublished - Nov 1 2015

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MicroRNAs
Extracellular Matrix
Peptide Hydrolases
Cortactin
Cell Line
Tyrosine
Phosphorylation
Neoplasm Metastasis
Recurrence
Messenger RNA
Proteins
Carcinoma, squamous cell of head and neck
Immunoprecipitation
Podosomes
Real-Time Polymerase Chain Reaction
Lymph Nodes
Western Blotting
Survival
Neoplasms

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology

Cite this

@article{9e52b00044cf4d41925f1ab669d24c9f,
title = "MicroRNA-375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma",
abstract = "Context.-Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an association with locoregional recurrence and lymph node metastasis. We have previously reported that low microRNA-375 (miR-375) expression levels correlate with poor patient survival, increased locoregional recurrence, and distant metastasis. Increasing miR-375 expression in HNSCC cell lines to levels found in normal cells results in suppressed invasive properties. HNSCC invasion is mediated in part by invadopodia-associated degradation of the extracellular matrix. Objective.-To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. Design.-For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of cortactin. Human protease arrays were used for the detection of the secreted proteases. Quantitative real time-polymerase chain reaction measurements were used to evaluate the messenger RNA (mRNA) expression of the commonly regulated proteases. Results.-Increased miR-375 expression in HNSCC cells suppresses extracellular matrix degradation and reduces the number of mature invadopodia. Higher miR-375 expression does not reduce cellular levels of selected invadopodia-associated proteins, nor is tyrosine phosphorylation of cortactin altered. However, HNSCC cells with higher miR-375 expression had significant reductions in the mRNA expression levels and secreted levels of specific proteases. Conclusions.-MicroRNA-375 regulates invadopodia maturation and function potentially by suppressing the expression and secretion of proteases.",
author = "Lizandra Jimenez and Sharma, {Ved P.} and Condeelis, {John S.} and Harris, {Thomas M.} and Ow, {Thomas J.} and Prystowsky, {Michael B.} and Childs, {Geoffrey J.} and Segall, {Jeffrey E.}",
year = "2015",
month = "11",
day = "1",
doi = "10.5858/arpa.2014-0471-OA",
language = "English (US)",
volume = "139",
pages = "1349--1361",
journal = "Archives of Pathology and Laboratory Medicine",
issn = "0003-9985",
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number = "11",

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T1 - MicroRNA-375 suppresses extracellular matrix degradation and invadopodial activity in head and neck squamous cell carcinoma

AU - Jimenez, Lizandra

AU - Sharma, Ved P.

AU - Condeelis, John S.

AU - Harris, Thomas M.

AU - Ow, Thomas J.

AU - Prystowsky, Michael B.

AU - Childs, Geoffrey J.

AU - Segall, Jeffrey E.

PY - 2015/11/1

Y1 - 2015/11/1

N2 - Context.-Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an association with locoregional recurrence and lymph node metastasis. We have previously reported that low microRNA-375 (miR-375) expression levels correlate with poor patient survival, increased locoregional recurrence, and distant metastasis. Increasing miR-375 expression in HNSCC cell lines to levels found in normal cells results in suppressed invasive properties. HNSCC invasion is mediated in part by invadopodia-associated degradation of the extracellular matrix. Objective.-To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. Design.-For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of cortactin. Human protease arrays were used for the detection of the secreted proteases. Quantitative real time-polymerase chain reaction measurements were used to evaluate the messenger RNA (mRNA) expression of the commonly regulated proteases. Results.-Increased miR-375 expression in HNSCC cells suppresses extracellular matrix degradation and reduces the number of mature invadopodia. Higher miR-375 expression does not reduce cellular levels of selected invadopodia-associated proteins, nor is tyrosine phosphorylation of cortactin altered. However, HNSCC cells with higher miR-375 expression had significant reductions in the mRNA expression levels and secreted levels of specific proteases. Conclusions.-MicroRNA-375 regulates invadopodia maturation and function potentially by suppressing the expression and secretion of proteases.

AB - Context.-Head and neck squamous cell carcinoma (HNSCC) is a highly invasive cancer with an association with locoregional recurrence and lymph node metastasis. We have previously reported that low microRNA-375 (miR-375) expression levels correlate with poor patient survival, increased locoregional recurrence, and distant metastasis. Increasing miR-375 expression in HNSCC cell lines to levels found in normal cells results in suppressed invasive properties. HNSCC invasion is mediated in part by invadopodia-associated degradation of the extracellular matrix. Objective.-To determine whether elevated miR-375 expression in HNSCC cell lines also affects invadopodia formation and activity. Design.-For evaluation of the matrix degradation properties of the HNSCC lines, an invadopodial matrix degradation assay was used. The total protein levels of invadopodia-associated proteins were measured by Western blot analyses. Immunoprecipitation experiments were conducted to evaluate the tyrosine phosphorylation state of cortactin. Human protease arrays were used for the detection of the secreted proteases. Quantitative real time-polymerase chain reaction measurements were used to evaluate the messenger RNA (mRNA) expression of the commonly regulated proteases. Results.-Increased miR-375 expression in HNSCC cells suppresses extracellular matrix degradation and reduces the number of mature invadopodia. Higher miR-375 expression does not reduce cellular levels of selected invadopodia-associated proteins, nor is tyrosine phosphorylation of cortactin altered. However, HNSCC cells with higher miR-375 expression had significant reductions in the mRNA expression levels and secreted levels of specific proteases. Conclusions.-MicroRNA-375 regulates invadopodia maturation and function potentially by suppressing the expression and secretion of proteases.

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SN - 0003-9985

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