Abstract

It has been suggested that stress stimuli from the microenvironment maintain a subset of tumor cells with stem-like properties, including drug resistance. Here, we investigate whether Sp1, a stress-responsive factor, regulates stemness gene expression and if its inhibition sensitizes cancer cells to chemotherapy. Hydrogen peroxide- and serum deprivation-induced stresses were performed in glioblastoma (GBM) cells and patient-derived cells, and the effect of the Sp1 inhibitor mithramycin A (MA) on these stress-induced stem cells and temozolomide (TMZ)-resistant cells was evaluated. Sp1 and stemness genes were not commonly overexpressed in clinical GBM samples. However, their expression was highly induced by stress stimuli. Using MA, we demonstrated Sp1 as a critical stemness-related transcriptional factor protecting GBM cells against stress- and TMZ-induced death. Thus, Sp1 inhibition may prevent recurrence of malignant cells persisting after primary therapy.

Original languageEnglish
Pages (from-to)14-19
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume493
Issue number1
DOIs
Publication statusPublished - Nov 4 2017

Fingerprint

Neoplasm Genes
Glioblastoma
Gene expression
Chemical activation
temozolomide
Gene Expression
Therapeutics
Cells
Chemotherapy
Neoplastic Stem Cells
Stem cells
Drug Resistance
Hydrogen Peroxide
Tumors
Stem Cells
Genes
Recurrence
Drug Therapy
Serum
Pharmaceutical Preparations

Keywords

  • Cancer stem cells
  • Glioblastoma
  • Mithramycin A
  • Sp1
  • Temozolomide

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Stress stimuli induce cancer-stemness gene expression via Sp1 activation leading to therapeutic resistance in glioblastoma. / Chang, Kwang Yu; Huang, Chih Ta; Hsu, Tsung I.; Hsu, Che Chia; Liu, Jr Jiun; Chuang, Cheng Keng; Hung, Jan Jong; Chang, Wen Chang; Tsai, Kelvin K.; Chuang, Jian Ying.

In: Biochemical and Biophysical Research Communications, Vol. 493, No. 1, 04.11.2017, p. 14-19.

Research output: Contribution to journalArticle

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AU - Chuang, Cheng Keng

AU - Hung, Jan Jong

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