Open Access

SLC7A5 regulates tryptophan uptake and PD‑L1 expression levels via the kynurenine pathway in ovarian cancer

  • Authors:
    • Ruibin Jiang
    • Bo Jin
    • Yuting Sun
    • Zhongjian Chen
    • Danying Wan
    • Jianguo Feng
    • Lisha Ying
    • Chanjuan Peng
    • Linhui Gu
  • View Affiliations

  • Published online on: October 24, 2024     https://doi.org/10.3892/ol.2024.14772
  • Article Number: 26
  • Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ovarian cancer is the third most common gynecological malignancy worldwide and the fifth leading cause of cancer‑related death among women. This may be attributed to difficulties in diagnosing early‑stage ovarian cancer, as it is typically asymptomatic until metastases, and due to the ineffective management of patients with late‑stage ovarian cancer. The aim of the present study was to investigate potential therapeutic targets for the treatment of ovarian cancer. Bioinformatics techniques were used to analyze the expression levels of tryptophan (Trp) metabolism‑related genes in tissue samples from patients with ovarian cancer. Additionally, western blots, clonogenic assays, immunohistochemical staining, chromatin immunoprecipitation‑quantitative PCR, cell co‑culture assays, a xenograft model and high‑performance liquid chromatography‑tandem mass spectrometry were performed to evaluate the antitumor effects of genes identified from the bioinformatics analysis. Increased expression levels of the amino acid transporter, solute carrier family 7 member 5 (SLC7A5), in tissue samples from patients with ovarian cancer was demonstrated. Inhibition of SLC7A5 reduced ovarian cancer cell proliferation through G2/M cell cycle arrest and blocked intracellular aryl hydrocarbon receptor nucleus entry, which downregulated PD‑L1 expression levels. Dysregulation of Trp metabolism in ovarian cancer tissue samples, as well as the upregulation of kynurenine expression levels in the plasma of patients with ovarian cancer, were demonstrated to be unfavorable prognostic factors for the progression‑free survival of patients with ovarian cancer. The present study demonstrated that the dysregulation of Trp metabolism could potentially be used as a diagnostic biomarker for ovarian cancer, as well as the potential of targeting SLC7A5 for immunotherapeutic management of patients with ovarian cancer in the future.
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January-2025
Volume 29 Issue 1

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Spandidos Publications style
Jiang R, Jin B, Sun Y, Chen Z, Wan D, Feng J, Ying L, Peng C and Gu L: SLC7A5 regulates tryptophan uptake and PD‑L1 expression levels via the kynurenine pathway in ovarian cancer. Oncol Lett 29: 26, 2025.
APA
Jiang, R., Jin, B., Sun, Y., Chen, Z., Wan, D., Feng, J. ... Gu, L. (2025). SLC7A5 regulates tryptophan uptake and PD‑L1 expression levels via the kynurenine pathway in ovarian cancer. Oncology Letters, 29, 26. https://doi.org/10.3892/ol.2024.14772
MLA
Jiang, R., Jin, B., Sun, Y., Chen, Z., Wan, D., Feng, J., Ying, L., Peng, C., Gu, L."SLC7A5 regulates tryptophan uptake and PD‑L1 expression levels via the kynurenine pathway in ovarian cancer". Oncology Letters 29.1 (2025): 26.
Chicago
Jiang, R., Jin, B., Sun, Y., Chen, Z., Wan, D., Feng, J., Ying, L., Peng, C., Gu, L."SLC7A5 regulates tryptophan uptake and PD‑L1 expression levels via the kynurenine pathway in ovarian cancer". Oncology Letters 29, no. 1 (2025): 26. https://doi.org/10.3892/ol.2024.14772