α-Actinin-4 regulates cancer stem cell properties and chemoresistance in cervical cancer

Jaeyeon Jung; Suhyun Kim; Hyoung Tae An; Jesang Ko

doi:10.1093/CARCIN/BGZ168

α-Actinin-4 regulates cancer stem cell properties and chemoresistance in cervical cancer

Jaeyeon Jung, Suhyun Kim, Hyoung Tae An, Jesang Ko

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

Cancer stem cells (CSCs) initiate tumors and possess the properties of self-renewal and differentiation. Since they are responsible for chemoresistance, CSCs are known to be a key factor in cancer recurrence. α-Actinin-4 (ACTN4) is an actin-binding protein that is involved in muscle differentiation and cancer metastasis. It promotes epithelial to mesenchymal transition and cell cycle progression via β-catenin stabilization in cervical cancer. In the present study, we investigated the role of ACTN4 in regulating cancer cell stemness and chemoresistance in cervical cancer. Results from the gene expression database analysis showed that ACTN4 mRNA expression was elevated in cancerous cervices when compared with normal cervices. Furthermore, ACTN4 knockdown suppressed sphere formation and CSC proliferation. It also decreased CSC size and CD44high/CD24^low cell population. ACTN4-knockdown CSCs were sensitive to anticancer drugs, which was observed by down-regulation of the ATP-binding cassette family G2 involved in drug resistance. Finally, ACTN4-knockdown CSCs formed reduced tumors in vivo when compared with control CSCs. Overall, these findings suggest that ACTN4 regulates CSC properties and contributes to chemoresistance in cervical cancer.

Original language	English
Pages (from-to)	940-949
Number of pages	10
Journal	Carcinogenesis
Volume	41
Issue number	7
DOIs	https://doi.org/10.1093/CARCIN/BGZ168
Publication status	Published - 2021

ASJC Scopus subject areas

Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/CARCIN/BGZ168

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title = "α-Actinin-4 regulates cancer stem cell properties and chemoresistance in cervical cancer",

abstract = "Cancer stem cells (CSCs) initiate tumors and possess the properties of self-renewal and differentiation. Since they are responsible for chemoresistance, CSCs are known to be a key factor in cancer recurrence. α-Actinin-4 (ACTN4) is an actin-binding protein that is involved in muscle differentiation and cancer metastasis. It promotes epithelial to mesenchymal transition and cell cycle progression via β-catenin stabilization in cervical cancer. In the present study, we investigated the role of ACTN4 in regulating cancer cell stemness and chemoresistance in cervical cancer. Results from the gene expression database analysis showed that ACTN4 mRNA expression was elevated in cancerous cervices when compared with normal cervices. Furthermore, ACTN4 knockdown suppressed sphere formation and CSC proliferation. It also decreased CSC size and CD44high/CD24low cell population. ACTN4-knockdown CSCs were sensitive to anticancer drugs, which was observed by down-regulation of the ATP-binding cassette family G2 involved in drug resistance. Finally, ACTN4-knockdown CSCs formed reduced tumors in vivo when compared with control CSCs. Overall, these findings suggest that ACTN4 regulates CSC properties and contributes to chemoresistance in cervical cancer.",

author = "Jaeyeon Jung and Suhyun Kim and An, {Hyoung Tae} and Jesang Ko",

note = "Funding Information: This work was supported by Tunneling Nanotube Research Center (NRF-2015R1A5A1009024) through the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIP) and the Korea University Grant. Conflict of Interest Statement: None declared. Publisher Copyright: {\textcopyright} The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.",

year = "2021",

doi = "10.1093/CARCIN/BGZ168",

language = "English",

volume = "41",

pages = "940--949",

journal = "Carcinogenesis",

issn = "0143-3334",

publisher = "Oxford University Press",

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TY - JOUR

T1 - α-Actinin-4 regulates cancer stem cell properties and chemoresistance in cervical cancer

AU - Jung, Jaeyeon

AU - Kim, Suhyun

AU - An, Hyoung Tae

AU - Ko, Jesang

N1 - Funding Information: This work was supported by Tunneling Nanotube Research Center (NRF-2015R1A5A1009024) through the National Research Foundation of Korea (NRF) grant funded by the Korea Government (MSIP) and the Korea University Grant. Conflict of Interest Statement: None declared. Publisher Copyright: © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

PY - 2021

Y1 - 2021

N2 - Cancer stem cells (CSCs) initiate tumors and possess the properties of self-renewal and differentiation. Since they are responsible for chemoresistance, CSCs are known to be a key factor in cancer recurrence. α-Actinin-4 (ACTN4) is an actin-binding protein that is involved in muscle differentiation and cancer metastasis. It promotes epithelial to mesenchymal transition and cell cycle progression via β-catenin stabilization in cervical cancer. In the present study, we investigated the role of ACTN4 in regulating cancer cell stemness and chemoresistance in cervical cancer. Results from the gene expression database analysis showed that ACTN4 mRNA expression was elevated in cancerous cervices when compared with normal cervices. Furthermore, ACTN4 knockdown suppressed sphere formation and CSC proliferation. It also decreased CSC size and CD44high/CD24low cell population. ACTN4-knockdown CSCs were sensitive to anticancer drugs, which was observed by down-regulation of the ATP-binding cassette family G2 involved in drug resistance. Finally, ACTN4-knockdown CSCs formed reduced tumors in vivo when compared with control CSCs. Overall, these findings suggest that ACTN4 regulates CSC properties and contributes to chemoresistance in cervical cancer.

AB - Cancer stem cells (CSCs) initiate tumors and possess the properties of self-renewal and differentiation. Since they are responsible for chemoresistance, CSCs are known to be a key factor in cancer recurrence. α-Actinin-4 (ACTN4) is an actin-binding protein that is involved in muscle differentiation and cancer metastasis. It promotes epithelial to mesenchymal transition and cell cycle progression via β-catenin stabilization in cervical cancer. In the present study, we investigated the role of ACTN4 in regulating cancer cell stemness and chemoresistance in cervical cancer. Results from the gene expression database analysis showed that ACTN4 mRNA expression was elevated in cancerous cervices when compared with normal cervices. Furthermore, ACTN4 knockdown suppressed sphere formation and CSC proliferation. It also decreased CSC size and CD44high/CD24low cell population. ACTN4-knockdown CSCs were sensitive to anticancer drugs, which was observed by down-regulation of the ATP-binding cassette family G2 involved in drug resistance. Finally, ACTN4-knockdown CSCs formed reduced tumors in vivo when compared with control CSCs. Overall, these findings suggest that ACTN4 regulates CSC properties and contributes to chemoresistance in cervical cancer.

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α-Actinin-4 regulates cancer stem cell properties and chemoresistance in cervical cancer

Abstract

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UN SDGs

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