HMGA1 silencing reduces stemness and temozolomide resistance in glioblastoma stem cells

Marianna Colamaio, Nadia Tosti, Francesca Puca, Alessia Mari, Rosaria Gattordo, Yalçın Kuzay, Antonella Federico, Anna Pepe, Daniela Sarnataro, Elvira Ragozzino, Maddalena Raia, Hidenari Hirata, Marica Gemei, Koshi Mimori, Luigi del Vecchio, Sabrina Battista, Alfredo Fusco

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Objective: Glioblastoma multiforme (GBM) develops from a small subpopulation of stem-like cells, which are endowed with the ability to self-renew, proliferate and give rise to progeny of multiple neuroepithelial lineages. These cells are resistant to conventional chemo- and radiotherapy and are hence also responsible for tumor recurrence. HMGA1 overexpression has been shown to correlate with proliferation, invasion, and angiogenesis of GBMs and to affect self-renewal of cancer stem cells from colon cancer. The role of HMGA1 in GBM tumor stem cells is not completely understood. Research design and methods: We have investigated the role of HMGA1 in brain tumor stem cell (BTSC) self-renewal, stemness and resistance to temozolomide by shRNA- mediated HMGA1 silencing. Results: We first report that HMGA1 is overexpressed in a subset of BTSC lines from human GBMs. Then, we show that HMGA1 knockdown reduces self-renewal, sphere forming efficiency and stemness, and sensitizes BTSCs to temozolomide. Interestingly, HMGA1 silencing also leads to reduced tumor initiation ability in vivo. Conclusions: These results demonstrate a pivotal role of HMGA1 in cancer stem cell gliomagenesis and endorse HMGA1 as a suitable target for CSC-specific GBM therapy.

Original languageEnglish
Pages (from-to)1169-1179
Number of pages11
JournalExpert Opinion on Therapeutic Targets
Volume20
Issue number10
DOIs
Publication statusPublished - Oct 2 2016

Fingerprint

temozolomide
Neoplastic Stem Cells
Glioblastoma
Stem cells
Tumors
Stem Cells
Brain Neoplasms
Brain
Chemotherapy
Radiotherapy
Tumor Cell Line
Colonic Neoplasms
Small Interfering RNA
Neoplasms
Research Design
Cells
Recurrence
Drug Therapy

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Colamaio, M., Tosti, N., Puca, F., Mari, A., Gattordo, R., Kuzay, Y., ... Fusco, A. (2016). HMGA1 silencing reduces stemness and temozolomide resistance in glioblastoma stem cells. Expert Opinion on Therapeutic Targets, 20(10), 1169-1179. https://doi.org/10.1080/14728222.2016.1220543

HMGA1 silencing reduces stemness and temozolomide resistance in glioblastoma stem cells. / Colamaio, Marianna; Tosti, Nadia; Puca, Francesca; Mari, Alessia; Gattordo, Rosaria; Kuzay, Yalçın; Federico, Antonella; Pepe, Anna; Sarnataro, Daniela; Ragozzino, Elvira; Raia, Maddalena; Hirata, Hidenari; Gemei, Marica; Mimori, Koshi; del Vecchio, Luigi; Battista, Sabrina; Fusco, Alfredo.

In: Expert Opinion on Therapeutic Targets, Vol. 20, No. 10, 02.10.2016, p. 1169-1179.

Research output: Contribution to journalArticle

Colamaio, M, Tosti, N, Puca, F, Mari, A, Gattordo, R, Kuzay, Y, Federico, A, Pepe, A, Sarnataro, D, Ragozzino, E, Raia, M, Hirata, H, Gemei, M, Mimori, K, del Vecchio, L, Battista, S & Fusco, A 2016, 'HMGA1 silencing reduces stemness and temozolomide resistance in glioblastoma stem cells', Expert Opinion on Therapeutic Targets, vol. 20, no. 10, pp. 1169-1179. https://doi.org/10.1080/14728222.2016.1220543
Colamaio, Marianna ; Tosti, Nadia ; Puca, Francesca ; Mari, Alessia ; Gattordo, Rosaria ; Kuzay, Yalçın ; Federico, Antonella ; Pepe, Anna ; Sarnataro, Daniela ; Ragozzino, Elvira ; Raia, Maddalena ; Hirata, Hidenari ; Gemei, Marica ; Mimori, Koshi ; del Vecchio, Luigi ; Battista, Sabrina ; Fusco, Alfredo. / HMGA1 silencing reduces stemness and temozolomide resistance in glioblastoma stem cells. In: Expert Opinion on Therapeutic Targets. 2016 ; Vol. 20, No. 10. pp. 1169-1179.
@article{0e5015fb9654473d8cbaa020f2a31c1e,
title = "HMGA1 silencing reduces stemness and temozolomide resistance in glioblastoma stem cells",
abstract = "Objective: Glioblastoma multiforme (GBM) develops from a small subpopulation of stem-like cells, which are endowed with the ability to self-renew, proliferate and give rise to progeny of multiple neuroepithelial lineages. These cells are resistant to conventional chemo- and radiotherapy and are hence also responsible for tumor recurrence. HMGA1 overexpression has been shown to correlate with proliferation, invasion, and angiogenesis of GBMs and to affect self-renewal of cancer stem cells from colon cancer. The role of HMGA1 in GBM tumor stem cells is not completely understood. Research design and methods: We have investigated the role of HMGA1 in brain tumor stem cell (BTSC) self-renewal, stemness and resistance to temozolomide by shRNA- mediated HMGA1 silencing. Results: We first report that HMGA1 is overexpressed in a subset of BTSC lines from human GBMs. Then, we show that HMGA1 knockdown reduces self-renewal, sphere forming efficiency and stemness, and sensitizes BTSCs to temozolomide. Interestingly, HMGA1 silencing also leads to reduced tumor initiation ability in vivo. Conclusions: These results demonstrate a pivotal role of HMGA1 in cancer stem cell gliomagenesis and endorse HMGA1 as a suitable target for CSC-specific GBM therapy.",
author = "Marianna Colamaio and Nadia Tosti and Francesca Puca and Alessia Mari and Rosaria Gattordo and Yal{\cc}ın Kuzay and Antonella Federico and Anna Pepe and Daniela Sarnataro and Elvira Ragozzino and Maddalena Raia and Hidenari Hirata and Marica Gemei and Koshi Mimori and {del Vecchio}, Luigi and Sabrina Battista and Alfredo Fusco",
year = "2016",
month = "10",
day = "2",
doi = "10.1080/14728222.2016.1220543",
language = "English",
volume = "20",
pages = "1169--1179",
journal = "Expert Opinion on Therapeutic Targets",
issn = "1472-8222",
publisher = "Informa Healthcare",
number = "10",

}

TY - JOUR

T1 - HMGA1 silencing reduces stemness and temozolomide resistance in glioblastoma stem cells

AU - Colamaio, Marianna

AU - Tosti, Nadia

AU - Puca, Francesca

AU - Mari, Alessia

AU - Gattordo, Rosaria

AU - Kuzay, Yalçın

AU - Federico, Antonella

AU - Pepe, Anna

AU - Sarnataro, Daniela

AU - Ragozzino, Elvira

AU - Raia, Maddalena

AU - Hirata, Hidenari

AU - Gemei, Marica

AU - Mimori, Koshi

AU - del Vecchio, Luigi

AU - Battista, Sabrina

AU - Fusco, Alfredo

PY - 2016/10/2

Y1 - 2016/10/2

N2 - Objective: Glioblastoma multiforme (GBM) develops from a small subpopulation of stem-like cells, which are endowed with the ability to self-renew, proliferate and give rise to progeny of multiple neuroepithelial lineages. These cells are resistant to conventional chemo- and radiotherapy and are hence also responsible for tumor recurrence. HMGA1 overexpression has been shown to correlate with proliferation, invasion, and angiogenesis of GBMs and to affect self-renewal of cancer stem cells from colon cancer. The role of HMGA1 in GBM tumor stem cells is not completely understood. Research design and methods: We have investigated the role of HMGA1 in brain tumor stem cell (BTSC) self-renewal, stemness and resistance to temozolomide by shRNA- mediated HMGA1 silencing. Results: We first report that HMGA1 is overexpressed in a subset of BTSC lines from human GBMs. Then, we show that HMGA1 knockdown reduces self-renewal, sphere forming efficiency and stemness, and sensitizes BTSCs to temozolomide. Interestingly, HMGA1 silencing also leads to reduced tumor initiation ability in vivo. Conclusions: These results demonstrate a pivotal role of HMGA1 in cancer stem cell gliomagenesis and endorse HMGA1 as a suitable target for CSC-specific GBM therapy.

AB - Objective: Glioblastoma multiforme (GBM) develops from a small subpopulation of stem-like cells, which are endowed with the ability to self-renew, proliferate and give rise to progeny of multiple neuroepithelial lineages. These cells are resistant to conventional chemo- and radiotherapy and are hence also responsible for tumor recurrence. HMGA1 overexpression has been shown to correlate with proliferation, invasion, and angiogenesis of GBMs and to affect self-renewal of cancer stem cells from colon cancer. The role of HMGA1 in GBM tumor stem cells is not completely understood. Research design and methods: We have investigated the role of HMGA1 in brain tumor stem cell (BTSC) self-renewal, stemness and resistance to temozolomide by shRNA- mediated HMGA1 silencing. Results: We first report that HMGA1 is overexpressed in a subset of BTSC lines from human GBMs. Then, we show that HMGA1 knockdown reduces self-renewal, sphere forming efficiency and stemness, and sensitizes BTSCs to temozolomide. Interestingly, HMGA1 silencing also leads to reduced tumor initiation ability in vivo. Conclusions: These results demonstrate a pivotal role of HMGA1 in cancer stem cell gliomagenesis and endorse HMGA1 as a suitable target for CSC-specific GBM therapy.

UR - http://www.scopus.com/inward/record.url?scp=84986237373&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84986237373&partnerID=8YFLogxK

U2 - 10.1080/14728222.2016.1220543

DO - 10.1080/14728222.2016.1220543

M3 - Article

VL - 20

SP - 1169

EP - 1179

JO - Expert Opinion on Therapeutic Targets

JF - Expert Opinion on Therapeutic Targets

SN - 1472-8222

IS - 10

ER -