Open Access

Co‑expression of SLC20A1 and ALDH1A3 is associated with poor prognosis, and SLC20A1 is required for the survival of ALDH1‑positive pancreatic cancer stem cells

  • Authors:
    • Izumi Matsuoka
    • Takahiro Kasai
    • Chotaro Onaga
    • Ayaka Ozaki
    • Hitomi Motomura
    • Yuki Maemura
    • Yuna Tada
    • Haruka Mori
    • Yasushi Hara
    • Yuyun Xiong
    • Keiko Sato
    • Shoma Tamori
    • Kazunori Sasaki
    • Shigeo Ohno
    • Kazunori Akimoto
  • View Affiliations

  • Published online on: July 5, 2024     https://doi.org/10.3892/ol.2024.14558
  • Article Number: 426
  • Copyright: © Matsuoka et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Solute carrier family 20 member 1 (SLC20A1) is a sodium/inorganic phosphate symporter, which has been identified as a prognostic marker in several types of cancer, including pancreatic cancer. However, to the best of our knowledge, the association between SLC20A1 expression and cancer stem cell (CSC) markers, such as aldehyde dehydrogenase 1 (ALDH1), in pancreatic ductal adenocarcinoma (PDAC), and the role of SLC20A1 in PDAC CSCs remains unclear. In the present study, a genomic dataset of primary pancreatic cancer (The Cancer Genome Atlas, Pan‑Cancer Atlas) was downloaded and analyzed. Kaplan‑Meier analysis and multivariate Cox regression analysis were performed to evaluate the overall survival, disease‑specific survival (DSS), disease‑free interval (DFI) and progression‑free interval (PFI). Subsequently, SLC20A1 small interfering RNA (siRNA) knockdown (KD) was induced in the PANC‑1 and MIA‑PaCa‑2 PDAC cell lines, and in sorted high ALDH1 activity (ALDH1high) cells, after which, cell viability, in vitro tumor sphere formation, cell death and caspase‑3 activity were examined. The results revealed that patients with high expression of SLC20A1 (SLC20A1high) at tumor stage I had a poor prognosis compared with patients with low expression of SLC20A1 (SLC20A1low) in terms of DSS, DFI and PFI. In addition, patients with high expression of SLC20A1 and ALDH1A3 (SLC20A1highALDH1A3high) exhibited poorer clinical outcomes than patients with high expression of SLC20A1 and low expression of ALDH1A3 (SLC20A1highALDH1A3low), low expression of SLC20A1 and high expression of ALDH1A3 (SLC20A1lowALDH1A3high) and SLC20A1lowALDH1A3low. SLC20A1 siRNA KD in ALDH1high cells isolated from PANC‑1 and MIA‑PaCa‑2 cell lines resulted in suppression of in vitro tumorsphere formation, and enhancement of cell death and caspase‑3 activity. These results suggested that SLC20A1 was involved in cell survival via the suppression of caspase‑3‑dependent apoptosis, and contributed to cancer progression and poor clinical outcomes in PDAC. In conclusion, SLC20A1 may be used as a prognostic marker and novel therapeutic target of ALDH1‑positive pancreatic CSCs.
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September-2024
Volume 28 Issue 3

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Spandidos Publications style
Matsuoka I, Kasai T, Onaga C, Ozaki A, Motomura H, Maemura Y, Tada Y, Mori H, Hara Y, Xiong Y, Xiong Y, et al: Co‑expression of <em>SLC20A1 </em>and <em>ALDH1A3</em> is associated with poor prognosis, and <em>SLC20A1 </em>is required for the survival of ALDH1‑positive pancreatic cancer stem cells. Oncol Lett 28: 426, 2024.
APA
Matsuoka, I., Kasai, T., Onaga, C., Ozaki, A., Motomura, H., Maemura, Y. ... Akimoto, K. (2024). Co‑expression of <em>SLC20A1 </em>and <em>ALDH1A3</em> is associated with poor prognosis, and <em>SLC20A1 </em>is required for the survival of ALDH1‑positive pancreatic cancer stem cells. Oncology Letters, 28, 426. https://doi.org/10.3892/ol.2024.14558
MLA
Matsuoka, I., Kasai, T., Onaga, C., Ozaki, A., Motomura, H., Maemura, Y., Tada, Y., Mori, H., Hara, Y., Xiong, Y., Sato, K., Tamori, S., Sasaki, K., Ohno, S., Akimoto, K."Co‑expression of <em>SLC20A1 </em>and <em>ALDH1A3</em> is associated with poor prognosis, and <em>SLC20A1 </em>is required for the survival of ALDH1‑positive pancreatic cancer stem cells". Oncology Letters 28.3 (2024): 426.
Chicago
Matsuoka, I., Kasai, T., Onaga, C., Ozaki, A., Motomura, H., Maemura, Y., Tada, Y., Mori, H., Hara, Y., Xiong, Y., Sato, K., Tamori, S., Sasaki, K., Ohno, S., Akimoto, K."Co‑expression of <em>SLC20A1 </em>and <em>ALDH1A3</em> is associated with poor prognosis, and <em>SLC20A1 </em>is required for the survival of ALDH1‑positive pancreatic cancer stem cells". Oncology Letters 28, no. 3 (2024): 426. https://doi.org/10.3892/ol.2024.14558