MSI1 associates glioblastoma radioresistance via homologous recombination repair, tumor invasion and cancer stem-like cell properties

Jang Chun Lin, Jo Ting Tsai, Tsu Yi Chao, Hsin I. Ma, Chian Shiu Chien, Wei Hsiu Liu

研究成果: 雜誌貢獻文章

5 引文 (Scopus)

摘要

Introduction: Glioblastoma multiforme (GBM) is the most common brain malignancy in adults, and currently available GBM treatments present several unique challenges. It is known that GBM involves cancer stem-like cells (CSCs) and tumor cells that aggressively invade normal brain tissues, and both cell types may cause resistance to radiotherapy (RT) and are thus responsible for therapeutic failure. The radioresistance of GBM cells relies on the efficient activation of the DNA damage response (DDR), but the mechanisms linking this response with stem-cell status and tumor invasion remain unclear. Materials and methods: We used irradiation to treat patient-derived GBM (Par) cells and then purified radioresistant GBM (R2M2) cells through two rounds of irradiation and an invasion assay. Musashi-1 (MSI1) is a neural stem-cell marker and key oncogenic factor of GBM. We identified MSI1 expression to predict radioresistance through silencing an MSI1-high-expressing R2M2 cell line or inducing overexpression in a Par cell line with low/no MSI1 expression and assessing the subsequent DDR. Result: MSI1 enhances tumor invasion via VCAM1 and modulates GBM radioresistance via the hyperactivation of the DDR through increasing homologous recombination repair and evading apoptosis. MSI1 knockdown induces DNA damage accumulation in irradiated GBM cells and promotes their depletion in vitro; MSI1 knockdown also inhibits the formation of GBMs generated by irradiated xeno-transplanted cells. MSI1 inhibition may radiosensitize tumors, prevent CSC-positive selection induced by RT, and reduce tumor invasion. Conclusion: MSI1 may involve in regulating GBM radioresistance, invasion, and recurrence and could be a novel target for GBM treatment.
原文英語
期刊Radiotherapy and Oncology
DOIs
出版狀態接受/付印 - 一月 1 2018

指紋

Recombinational DNA Repair
Neoplastic Stem Cells
Glioblastoma
Neoplasms
DNA Damage
Radiotherapy
Cell Line
Neural Stem Cells
Brain
Therapeutics

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

引用此文

@article{27e1e3c0644b4625a3c686239d66071b,
title = "MSI1 associates glioblastoma radioresistance via homologous recombination repair, tumor invasion and cancer stem-like cell properties",
abstract = "Introduction: Glioblastoma multiforme (GBM) is the most common brain malignancy in adults, and currently available GBM treatments present several unique challenges. It is known that GBM involves cancer stem-like cells (CSCs) and tumor cells that aggressively invade normal brain tissues, and both cell types may cause resistance to radiotherapy (RT) and are thus responsible for therapeutic failure. The radioresistance of GBM cells relies on the efficient activation of the DNA damage response (DDR), but the mechanisms linking this response with stem-cell status and tumor invasion remain unclear. Materials and methods: We used irradiation to treat patient-derived GBM (Par) cells and then purified radioresistant GBM (R2M2) cells through two rounds of irradiation and an invasion assay. Musashi-1 (MSI1) is a neural stem-cell marker and key oncogenic factor of GBM. We identified MSI1 expression to predict radioresistance through silencing an MSI1-high-expressing R2M2 cell line or inducing overexpression in a Par cell line with low/no MSI1 expression and assessing the subsequent DDR. Result: MSI1 enhances tumor invasion via VCAM1 and modulates GBM radioresistance via the hyperactivation of the DDR through increasing homologous recombination repair and evading apoptosis. MSI1 knockdown induces DNA damage accumulation in irradiated GBM cells and promotes their depletion in vitro; MSI1 knockdown also inhibits the formation of GBMs generated by irradiated xeno-transplanted cells. MSI1 inhibition may radiosensitize tumors, prevent CSC-positive selection induced by RT, and reduce tumor invasion. Conclusion: MSI1 may involve in regulating GBM radioresistance, invasion, and recurrence and could be a novel target for GBM treatment.",
keywords = "Cancer stem-like cells (CSCs), Glioblastoma (GBM), Musashi-1 (MSI1), Radiotherapy (RT)",
author = "Lin, {Jang Chun} and Tsai, {Jo Ting} and Chao, {Tsu Yi} and Ma, {Hsin I.} and Chien, {Chian Shiu} and Liu, {Wei Hsiu}",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.radonc.2018.09.014",
language = "English",
journal = "Radiotherapy and Oncology",
issn = "0167-8140",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - MSI1 associates glioblastoma radioresistance via homologous recombination repair, tumor invasion and cancer stem-like cell properties

AU - Lin, Jang Chun

AU - Tsai, Jo Ting

AU - Chao, Tsu Yi

AU - Ma, Hsin I.

AU - Chien, Chian Shiu

AU - Liu, Wei Hsiu

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Introduction: Glioblastoma multiforme (GBM) is the most common brain malignancy in adults, and currently available GBM treatments present several unique challenges. It is known that GBM involves cancer stem-like cells (CSCs) and tumor cells that aggressively invade normal brain tissues, and both cell types may cause resistance to radiotherapy (RT) and are thus responsible for therapeutic failure. The radioresistance of GBM cells relies on the efficient activation of the DNA damage response (DDR), but the mechanisms linking this response with stem-cell status and tumor invasion remain unclear. Materials and methods: We used irradiation to treat patient-derived GBM (Par) cells and then purified radioresistant GBM (R2M2) cells through two rounds of irradiation and an invasion assay. Musashi-1 (MSI1) is a neural stem-cell marker and key oncogenic factor of GBM. We identified MSI1 expression to predict radioresistance through silencing an MSI1-high-expressing R2M2 cell line or inducing overexpression in a Par cell line with low/no MSI1 expression and assessing the subsequent DDR. Result: MSI1 enhances tumor invasion via VCAM1 and modulates GBM radioresistance via the hyperactivation of the DDR through increasing homologous recombination repair and evading apoptosis. MSI1 knockdown induces DNA damage accumulation in irradiated GBM cells and promotes their depletion in vitro; MSI1 knockdown also inhibits the formation of GBMs generated by irradiated xeno-transplanted cells. MSI1 inhibition may radiosensitize tumors, prevent CSC-positive selection induced by RT, and reduce tumor invasion. Conclusion: MSI1 may involve in regulating GBM radioresistance, invasion, and recurrence and could be a novel target for GBM treatment.

AB - Introduction: Glioblastoma multiforme (GBM) is the most common brain malignancy in adults, and currently available GBM treatments present several unique challenges. It is known that GBM involves cancer stem-like cells (CSCs) and tumor cells that aggressively invade normal brain tissues, and both cell types may cause resistance to radiotherapy (RT) and are thus responsible for therapeutic failure. The radioresistance of GBM cells relies on the efficient activation of the DNA damage response (DDR), but the mechanisms linking this response with stem-cell status and tumor invasion remain unclear. Materials and methods: We used irradiation to treat patient-derived GBM (Par) cells and then purified radioresistant GBM (R2M2) cells through two rounds of irradiation and an invasion assay. Musashi-1 (MSI1) is a neural stem-cell marker and key oncogenic factor of GBM. We identified MSI1 expression to predict radioresistance through silencing an MSI1-high-expressing R2M2 cell line or inducing overexpression in a Par cell line with low/no MSI1 expression and assessing the subsequent DDR. Result: MSI1 enhances tumor invasion via VCAM1 and modulates GBM radioresistance via the hyperactivation of the DDR through increasing homologous recombination repair and evading apoptosis. MSI1 knockdown induces DNA damage accumulation in irradiated GBM cells and promotes their depletion in vitro; MSI1 knockdown also inhibits the formation of GBMs generated by irradiated xeno-transplanted cells. MSI1 inhibition may radiosensitize tumors, prevent CSC-positive selection induced by RT, and reduce tumor invasion. Conclusion: MSI1 may involve in regulating GBM radioresistance, invasion, and recurrence and could be a novel target for GBM treatment.

KW - Cancer stem-like cells (CSCs)

KW - Glioblastoma (GBM)

KW - Musashi-1 (MSI1)

KW - Radiotherapy (RT)

UR - http://www.scopus.com/inward/record.url?scp=85054605375&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054605375&partnerID=8YFLogxK

U2 - 10.1016/j.radonc.2018.09.014

DO - 10.1016/j.radonc.2018.09.014

M3 - Article

AN - SCOPUS:85054605375

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

SN - 0167-8140

ER -