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HMGA1 stimulates cancer stem-like features and sensitivity to monensin in gastric cancer

Pádua, Diana ; Figueira, Paula ; Pombinho, António ; Monteiro, Inês ; Pereira, Carlos Filipe LU orcid ; Almeida, Raquel and Mesquita, Patrícia (2024) In Experimental Cell Research 442(2).
Abstract

Gastric cancer represents a serious health problem worldwide, with insufficient molecular biomarkers and therapeutic options. Consequently, several efforts have been directed towards finding specific disease markers in order to develop new therapies capable of defeating gastric cancer. Attention has been pointed to cancer stem cells (CSCs) as they are primarily responsible for tumor initiation and recurrence, making them essential therapeutic targets. Using the SORE6-GFP reporter system, based on the expression of SOX2 and/or OCT4 to drive GFP expression, we isolated gastric cancer stem-like cells (SORE6+ cells) enriched in several molecules, including SOX2, C-MYC, KLF4, HIF-1α, NOTCH1 and HMGA1. Here, we explored the previously... (More)

Gastric cancer represents a serious health problem worldwide, with insufficient molecular biomarkers and therapeutic options. Consequently, several efforts have been directed towards finding specific disease markers in order to develop new therapies capable of defeating gastric cancer. Attention has been pointed to cancer stem cells (CSCs) as they are primarily responsible for tumor initiation and recurrence, making them essential therapeutic targets. Using the SORE6-GFP reporter system, based on the expression of SOX2 and/or OCT4 to drive GFP expression, we isolated gastric cancer stem-like cells (SORE6+ cells) enriched in several molecules, including SOX2, C-MYC, KLF4, HIF-1α, NOTCH1 and HMGA1. Here, we explored the previously undisclosed link of HMGA1 with gastric CSCs. Our results indicated that HMGA1 can activate a transcriptional program that includes SOX2, C-MYC, and KLF4 and endows cells with CSC features. We further showed that chemical induction of gastric CSCs using ciclopirox (CPX) can be mediated by HMGA1. Finally, we showed that HMGA1 GFP+ cells were sensitive to monensin confirming the selective activity of this drug over CSCs. Thus, HMGA1 is a key player in the cellular reprogramming of gastric non-CSCs to cancer stem-like cells.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cellular reprogramming, Drug resistance, Monensin, SOX2, Transcription factors
in
Experimental Cell Research
volume
442
issue
2
article number
114257
publisher
Academic Press
external identifiers
  • scopus:85203980784
  • pmid:39293524
ISSN
0014-4827
DOI
10.1016/j.yexcr.2024.114257
language
English
LU publication?
yes
id
8d93f129-d2d1-424e-b10c-a9911422f51f
date added to LUP
2024-11-19 11:48:24
date last changed
2025-07-30 08:30:17
@article{8d93f129-d2d1-424e-b10c-a9911422f51f,
  abstract     = {{<p>Gastric cancer represents a serious health problem worldwide, with insufficient molecular biomarkers and therapeutic options. Consequently, several efforts have been directed towards finding specific disease markers in order to develop new therapies capable of defeating gastric cancer. Attention has been pointed to cancer stem cells (CSCs) as they are primarily responsible for tumor initiation and recurrence, making them essential therapeutic targets. Using the SORE6-GFP reporter system, based on the expression of SOX2 and/or OCT4 to drive GFP expression, we isolated gastric cancer stem-like cells (SORE6+ cells) enriched in several molecules, including SOX2, C-MYC, KLF4, HIF-1α, NOTCH1 and HMGA1. Here, we explored the previously undisclosed link of HMGA1 with gastric CSCs. Our results indicated that HMGA1 can activate a transcriptional program that includes SOX2, C-MYC, and KLF4 and endows cells with CSC features. We further showed that chemical induction of gastric CSCs using ciclopirox (CPX) can be mediated by HMGA1. Finally, we showed that HMGA1 GFP+ cells were sensitive to monensin confirming the selective activity of this drug over CSCs. Thus, HMGA1 is a key player in the cellular reprogramming of gastric non-CSCs to cancer stem-like cells.</p>}},
  author       = {{Pádua, Diana and Figueira, Paula and Pombinho, António and Monteiro, Inês and Pereira, Carlos Filipe and Almeida, Raquel and Mesquita, Patrícia}},
  issn         = {{0014-4827}},
  keywords     = {{Cellular reprogramming; Drug resistance; Monensin; SOX2; Transcription factors}},
  language     = {{eng}},
  number       = {{2}},
  publisher    = {{Academic Press}},
  series       = {{Experimental Cell Research}},
  title        = {{HMGA1 stimulates cancer stem-like features and sensitivity to monensin in gastric cancer}},
  url          = {{http://dx.doi.org/10.1016/j.yexcr.2024.114257}},
  doi          = {{10.1016/j.yexcr.2024.114257}},
  volume       = {{442}},
  year         = {{2024}},
}