Centrosome clustering is a tumor-selective target for the improvement of radiotherapy in breast cancer cells

Min Ho Choe, Joon Kim, Jiyeon Ahn, Sang Gu Hwang, Jeong Su Oh, Jae Sung Kim

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background/Aim: Owing to the frequent observation of centrosome amplification in human cancers, cancer cells have a unique mechanism to suppress detrimental multipolar division by clustering multiple centrosomes into two functional spindle poles, known as centrosome clustering. This study investigated whether inhibition of centrosome clustering enhances the radiation sensitivity of breast cancer cells. Materials and Methods: In this study, inhibition of centrosome clustering was examined by using various centrosome-declustering agents and KIFC1 siRNA in three breast cancer cell lines and two normal fibroblast cell lines. The combination effect of radiation and centrosome declustering was evaluated by cell viability, clonogenic, immunofluorescence assay. Results: This study showed that targeting centrosome clustering enhanced the efficacy of radiotherapy of breast cancer cells with less damage to normal cells. Ionizing radiation induced centrosome amplification in breast cancer cells, but not in normal fibroblast cells. Notably, we showed that centrosome declustering efficiently radiosensitized the centrosome-amplified breast cancer cells through induction of multipolar spindles but did not affect the viability of normal fibroblasts in response to irradiation. Furthermore, KIFC1 mediated the radiosensitivity of the centrosome-amplified breast cancer cells. Conclusion: Our data provided the first evidence that centrosome clustering is a tumor-selective target for the improvement of radiotherapy in breast cancer cells.

Original languageEnglish
Pages (from-to)3393-3400
Number of pages8
JournalAnticancer research
Volume38
Issue number6
DOIs
Publication statusPublished - 2018 Jun 1

Fingerprint

Centrosome
Cluster Analysis
Radiotherapy
Breast Neoplasms
Neoplasms
Fibroblasts
Radiation Tolerance
Spindle Poles
Cell Line
Radiation Effects
Ionizing Radiation
Small Interfering RNA
Fluorescent Antibody Technique
Cell Survival

Keywords

  • Breast cancer
  • Centrosome amplification
  • Centrosome clustering
  • Radiosensitizer
  • Radiotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Centrosome clustering is a tumor-selective target for the improvement of radiotherapy in breast cancer cells. / Choe, Min Ho; Kim, Joon; Ahn, Jiyeon; Hwang, Sang Gu; Oh, Jeong Su; Kim, Jae Sung.

In: Anticancer research, Vol. 38, No. 6, 01.06.2018, p. 3393-3400.

Research output: Contribution to journalArticle

Choe, Min Ho ; Kim, Joon ; Ahn, Jiyeon ; Hwang, Sang Gu ; Oh, Jeong Su ; Kim, Jae Sung. / Centrosome clustering is a tumor-selective target for the improvement of radiotherapy in breast cancer cells. In: Anticancer research. 2018 ; Vol. 38, No. 6. pp. 3393-3400.
@article{9182f2364b164e26913710bdccee3afe,
title = "Centrosome clustering is a tumor-selective target for the improvement of radiotherapy in breast cancer cells",
abstract = "Background/Aim: Owing to the frequent observation of centrosome amplification in human cancers, cancer cells have a unique mechanism to suppress detrimental multipolar division by clustering multiple centrosomes into two functional spindle poles, known as centrosome clustering. This study investigated whether inhibition of centrosome clustering enhances the radiation sensitivity of breast cancer cells. Materials and Methods: In this study, inhibition of centrosome clustering was examined by using various centrosome-declustering agents and KIFC1 siRNA in three breast cancer cell lines and two normal fibroblast cell lines. The combination effect of radiation and centrosome declustering was evaluated by cell viability, clonogenic, immunofluorescence assay. Results: This study showed that targeting centrosome clustering enhanced the efficacy of radiotherapy of breast cancer cells with less damage to normal cells. Ionizing radiation induced centrosome amplification in breast cancer cells, but not in normal fibroblast cells. Notably, we showed that centrosome declustering efficiently radiosensitized the centrosome-amplified breast cancer cells through induction of multipolar spindles but did not affect the viability of normal fibroblasts in response to irradiation. Furthermore, KIFC1 mediated the radiosensitivity of the centrosome-amplified breast cancer cells. Conclusion: Our data provided the first evidence that centrosome clustering is a tumor-selective target for the improvement of radiotherapy in breast cancer cells.",
keywords = "Breast cancer, Centrosome amplification, Centrosome clustering, Radiosensitizer, Radiotherapy",
author = "Choe, {Min Ho} and Joon Kim and Jiyeon Ahn and Hwang, {Sang Gu} and Oh, {Jeong Su} and Kim, {Jae Sung}",
year = "2018",
month = "6",
day = "1",
doi = "10.21873/anticanres.12606",
language = "English",
volume = "38",
pages = "3393--3400",
journal = "Anticancer Research",
issn = "0250-7005",
publisher = "International Institute of Anticancer Research",
number = "6",

}

TY - JOUR

T1 - Centrosome clustering is a tumor-selective target for the improvement of radiotherapy in breast cancer cells

AU - Choe, Min Ho

AU - Kim, Joon

AU - Ahn, Jiyeon

AU - Hwang, Sang Gu

AU - Oh, Jeong Su

AU - Kim, Jae Sung

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Background/Aim: Owing to the frequent observation of centrosome amplification in human cancers, cancer cells have a unique mechanism to suppress detrimental multipolar division by clustering multiple centrosomes into two functional spindle poles, known as centrosome clustering. This study investigated whether inhibition of centrosome clustering enhances the radiation sensitivity of breast cancer cells. Materials and Methods: In this study, inhibition of centrosome clustering was examined by using various centrosome-declustering agents and KIFC1 siRNA in three breast cancer cell lines and two normal fibroblast cell lines. The combination effect of radiation and centrosome declustering was evaluated by cell viability, clonogenic, immunofluorescence assay. Results: This study showed that targeting centrosome clustering enhanced the efficacy of radiotherapy of breast cancer cells with less damage to normal cells. Ionizing radiation induced centrosome amplification in breast cancer cells, but not in normal fibroblast cells. Notably, we showed that centrosome declustering efficiently radiosensitized the centrosome-amplified breast cancer cells through induction of multipolar spindles but did not affect the viability of normal fibroblasts in response to irradiation. Furthermore, KIFC1 mediated the radiosensitivity of the centrosome-amplified breast cancer cells. Conclusion: Our data provided the first evidence that centrosome clustering is a tumor-selective target for the improvement of radiotherapy in breast cancer cells.

AB - Background/Aim: Owing to the frequent observation of centrosome amplification in human cancers, cancer cells have a unique mechanism to suppress detrimental multipolar division by clustering multiple centrosomes into two functional spindle poles, known as centrosome clustering. This study investigated whether inhibition of centrosome clustering enhances the radiation sensitivity of breast cancer cells. Materials and Methods: In this study, inhibition of centrosome clustering was examined by using various centrosome-declustering agents and KIFC1 siRNA in three breast cancer cell lines and two normal fibroblast cell lines. The combination effect of radiation and centrosome declustering was evaluated by cell viability, clonogenic, immunofluorescence assay. Results: This study showed that targeting centrosome clustering enhanced the efficacy of radiotherapy of breast cancer cells with less damage to normal cells. Ionizing radiation induced centrosome amplification in breast cancer cells, but not in normal fibroblast cells. Notably, we showed that centrosome declustering efficiently radiosensitized the centrosome-amplified breast cancer cells through induction of multipolar spindles but did not affect the viability of normal fibroblasts in response to irradiation. Furthermore, KIFC1 mediated the radiosensitivity of the centrosome-amplified breast cancer cells. Conclusion: Our data provided the first evidence that centrosome clustering is a tumor-selective target for the improvement of radiotherapy in breast cancer cells.

KW - Breast cancer

KW - Centrosome amplification

KW - Centrosome clustering

KW - Radiosensitizer

KW - Radiotherapy

UR - http://www.scopus.com/inward/record.url?scp=85048213003&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048213003&partnerID=8YFLogxK

U2 - 10.21873/anticanres.12606

DO - 10.21873/anticanres.12606

M3 - Article

C2 - 29848688

AN - SCOPUS:85048213003

VL - 38

SP - 3393

EP - 3400

JO - Anticancer Research

JF - Anticancer Research

SN - 0250-7005

IS - 6

ER -