The Activity of KIF14, Mieap, and EZR in a New Type of the Invasive Component, Torpedo-Like Structures, Predetermines the Metastatic Potential of Breast Cancer

Intratumor morphological heterogeneity reflects patterns of invasive growth and is an indicator of the metastatic potential of breast cancer. In this study, we used this heterogeneity to identify molecules associated with breast cancer invasion and metastasis. The gene expression microarray data wer...

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Main Authors: Tatiana S. Gerashchenko, Sofia Y. Zolotaryova, Artem M. Kiselev, Liubov A. Tashireva, Nikita M. Novikov, Nadezhda V. Krakhmal, Nadezhda V. Cherdyntseva, Marina V. Zavyalova, Vladimir M. Perelmuter, Evgeny V. Denisov
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/12/7/1909
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author Tatiana S. Gerashchenko
Sofia Y. Zolotaryova
Artem M. Kiselev
Liubov A. Tashireva
Nikita M. Novikov
Nadezhda V. Krakhmal
Nadezhda V. Cherdyntseva
Marina V. Zavyalova
Vladimir M. Perelmuter
Evgeny V. Denisov
author_facet Tatiana S. Gerashchenko
Sofia Y. Zolotaryova
Artem M. Kiselev
Liubov A. Tashireva
Nikita M. Novikov
Nadezhda V. Krakhmal
Nadezhda V. Cherdyntseva
Marina V. Zavyalova
Vladimir M. Perelmuter
Evgeny V. Denisov
author_sort Tatiana S. Gerashchenko
collection DOAJ
description Intratumor morphological heterogeneity reflects patterns of invasive growth and is an indicator of the metastatic potential of breast cancer. In this study, we used this heterogeneity to identify molecules associated with breast cancer invasion and metastasis. The gene expression microarray data were used to identify genes differentially expressed between solid, trabecular, and other morphological arrangements of tumor cells. Immunohistochemistry was applied to evaluate the association of the selected proteins with metastasis. RNA-sequencing was performed to analyze the molecular makeup of metastatic tumor cells. High frequency of metastases and decreased metastasis-free survival were detected in patients either with positive expression of KIF14 or Mieap or negative expression of EZR at the tips of the torpedo-like structures in breast cancers. KIF14- and Mieap-positive and EZR-negative cells were mainly detected in the torpedo-like structures of the same breast tumors; however, their transcriptomic features differed. KIF14-positive cells showed a significant upregulation of genes involved in ether lipid metabolism. Mieap-positive cells were enriched in genes involved in mitophagy. EZR-negative cells displayed upregulated genes associated with phagocytosis and the chemokine-mediated signaling pathway. In conclusion, the positive expression of KIF14 and Mieap and negative expression of EZR at the tips of the torpedo-like structures are associated with breast cancer metastasis.
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spelling doaj.art-9ad702c7133248e4aa0a01b582656cd02023-11-20T06:51:16ZengMDPI AGCancers2072-66942020-07-01127190910.3390/cancers12071909The Activity of KIF14, Mieap, and EZR in a New Type of the Invasive Component, Torpedo-Like Structures, Predetermines the Metastatic Potential of Breast CancerTatiana S. Gerashchenko0Sofia Y. Zolotaryova1Artem M. Kiselev2Liubov A. Tashireva3Nikita M. Novikov4Nadezhda V. Krakhmal5Nadezhda V. Cherdyntseva6Marina V. Zavyalova7Vladimir M. Perelmuter8Evgeny V. Denisov9Laboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, RussiaLaboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, RussiaLaboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, RussiaDepartment of General and Molecular Pathology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, RussiaLaboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, RussiaDepartment of Pathological Anatomy, Siberian State Medical University, 634050 Tomsk, RussiaLaboratory of Molecular Oncology and Immunology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, RussiaDepartment of General and Molecular Pathology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, RussiaDepartment of General and Molecular Pathology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, RussiaLaboratory of Cancer Progression Biology, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, 634009 Tomsk, RussiaIntratumor morphological heterogeneity reflects patterns of invasive growth and is an indicator of the metastatic potential of breast cancer. In this study, we used this heterogeneity to identify molecules associated with breast cancer invasion and metastasis. The gene expression microarray data were used to identify genes differentially expressed between solid, trabecular, and other morphological arrangements of tumor cells. Immunohistochemistry was applied to evaluate the association of the selected proteins with metastasis. RNA-sequencing was performed to analyze the molecular makeup of metastatic tumor cells. High frequency of metastases and decreased metastasis-free survival were detected in patients either with positive expression of KIF14 or Mieap or negative expression of EZR at the tips of the torpedo-like structures in breast cancers. KIF14- and Mieap-positive and EZR-negative cells were mainly detected in the torpedo-like structures of the same breast tumors; however, their transcriptomic features differed. KIF14-positive cells showed a significant upregulation of genes involved in ether lipid metabolism. Mieap-positive cells were enriched in genes involved in mitophagy. EZR-negative cells displayed upregulated genes associated with phagocytosis and the chemokine-mediated signaling pathway. In conclusion, the positive expression of KIF14 and Mieap and negative expression of EZR at the tips of the torpedo-like structures are associated with breast cancer metastasis.https://www.mdpi.com/2072-6694/12/7/1909breast cancermetastasisinvasionheterogeneitymorphologytorpedo-like structures
spellingShingle Tatiana S. Gerashchenko
Sofia Y. Zolotaryova
Artem M. Kiselev
Liubov A. Tashireva
Nikita M. Novikov
Nadezhda V. Krakhmal
Nadezhda V. Cherdyntseva
Marina V. Zavyalova
Vladimir M. Perelmuter
Evgeny V. Denisov
The Activity of KIF14, Mieap, and EZR in a New Type of the Invasive Component, Torpedo-Like Structures, Predetermines the Metastatic Potential of Breast Cancer
Cancers
breast cancer
metastasis
invasion
heterogeneity
morphology
torpedo-like structures
title The Activity of KIF14, Mieap, and EZR in a New Type of the Invasive Component, Torpedo-Like Structures, Predetermines the Metastatic Potential of Breast Cancer
title_full The Activity of KIF14, Mieap, and EZR in a New Type of the Invasive Component, Torpedo-Like Structures, Predetermines the Metastatic Potential of Breast Cancer
title_fullStr The Activity of KIF14, Mieap, and EZR in a New Type of the Invasive Component, Torpedo-Like Structures, Predetermines the Metastatic Potential of Breast Cancer
title_full_unstemmed The Activity of KIF14, Mieap, and EZR in a New Type of the Invasive Component, Torpedo-Like Structures, Predetermines the Metastatic Potential of Breast Cancer
title_short The Activity of KIF14, Mieap, and EZR in a New Type of the Invasive Component, Torpedo-Like Structures, Predetermines the Metastatic Potential of Breast Cancer
title_sort activity of kif14 mieap and ezr in a new type of the invasive component torpedo like structures predetermines the metastatic potential of breast cancer
topic breast cancer
metastasis
invasion
heterogeneity
morphology
torpedo-like structures
url https://www.mdpi.com/2072-6694/12/7/1909
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