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Peer-reviewedCC BY-NCCancer science

Dietary Leucine Restriction Suppresses Platelet-Driven HCC Growth by Attenuating mTOR Signaling.

  • Xeulian Ruan1
  • Guiyong Ou2
  • Cuiju Mo3
  • Yi Zhang3
  • Shanzi Qin1
  • Yongling Chen4
  • Dan Li3
  • Liuying Nie2
  • Li Xie1
  • Zuojian Hu1
4 affiliations
  1. 1Department of Clinical Laboratory, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
  2. 2Department of Blood Transfusion, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
  3. 3Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University; Key Laboratory of Clinical Laboratory Medicine of Guangxi Department of Education, Nanning, Guangxi, China.
  4. 4Department of Blood Transfusion, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
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Abstract

Platelets play a crucial role in regulating tumor progression, but the mechanisms underlying platelet-induced metabolic reprogramming in hepatocellular carcinoma (HCC) remain incompletely understood. Here, metabolomic profiling identified significant accumulation of leucine in HCC cells following platelet incubation. Co-culture with platelets promoted HCC cell proliferation, migration, and invasion in complete medium, whereas leucine deprivation in the co-culture medium attenuated these malignant behaviors. Mechanistically, platelets selectively stimulated the phosphorylation of S6K1 and downstream S6, an activation that was suppressed under leucine-deficient conditions. In addition, pharmacological inhibition of S6K1 activity using PF-4708671 reduced platelet-promoted cellular proliferation, migration, and invasion, confirming the S6K1/S6 axis as an essential functional effector of this response. In vivo, dietary leucine restriction reduced tumor growth following platelet pre-incubation in the MHCC-97H xenograft model. Together, these findings demonstrate that leucine accumulation and subsequent S6K1/S6 activation mediate platelet-promoted HCC progression, indicating that targeting leucine availability or S6K1 signaling may offer therapeutic strategies for platelet-associated HCC.

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Cite

BibTeXRIS
BibTeX
@article{ruan2026dietary,
  title = {{Dietary Leucine Restriction Suppresses Platelet-Driven HCC Growth by Attenuating mTOR Signaling.}},
  author = {Xeulian Ruan and Guiyong Ou and Cuiju Mo and Yi Zhang and Shanzi Qin and Yongling Chen and Dan Li and Liuying Nie and Li Xie and Zuojian Hu},
  journal = {Cancer science},
  year = {2026},
  month = oct,
  doi = {10.1111/cas.70574},
  url = {https://europepmc.org/article/MED/42952101},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Dietary Leucine Restriction Suppresses Platelet-Driven HCC Growth by Attenuating mTOR Signaling.
AU  - Xeulian Ruan
AU  - Guiyong Ou
AU  - Cuiju Mo
AU  - Yi Zhang
AU  - Shanzi Qin
AU  - Yongling Chen
AU  - Dan Li
AU  - Liuying Nie
AU  - Li Xie
AU  - Zuojian Hu
PY  - 2026
DA  - 2026/10/28
JO  - Cancer science
DO  - 10.1111/cas.70574
UR  - https://europepmc.org/article/MED/42952101
AB  - Platelets play a crucial role in regulating tumor progression, but the mechanisms underlying platelet-induced metabolic reprogramming in hepatocellular carcinoma (HCC) remain incompletely understood. Here, metabolomic profiling identified significant accumulation of leucine in HCC cells following platelet incubation. Co-culture with platelets promoted HCC cell proliferation, migration, and invasion in complete medium, whereas leucine deprivation in the co-culture medium attenuated these malignant behaviors. Mechanistically, platelets selectively stimulated the phosphorylation of S6K1 and downstream S6, an activation that was suppressed under leucine-deficient conditions. In addition, pharmacological inhibition of S6K1 activity using PF-4708671 reduced platelet-promoted cellular proliferation, migration, and invasion, confirming the S6K1/S6 axis as an essential functional effector of this response. In vivo, dietary leucine restriction reduced tumor growth following platelet pre-incubation in the MHCC-97H xenograft model. Together, these findings demonstrate that leucine accumulation and subsequent S6K1/S6 activation mediate platelet-promoted HCC progression, indicating that targeting leucine availability or S6K1 signaling may offer therapeutic strategies for platelet-associated HCC.
SN  - 1347-9032
SN  - 1349-7006
ER  -