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PDLIM1 interacts with HK2 to promote gastric cancer progression through enhancing the Warburg effect via Wnt/β-catenin signaling

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Abstract

PDZ and LIM domain protein 1 (PDLIM1) is a cytoskeletal protein and is associated with the malignant pathological features of several tumors. However, the prognostic value of PDLIM1 and the molecular mechanisms by which it is involved in the metabolism and progression in gastric cancer (GC) are still unclear. The GEPIA database was used to predict the expression and prognosis of PDLIM1 in GC. qRT-PCR and western blot assays were applied to detect the mRNA and protein expression in GC tissues and cells. Loss- and gain-of-function experiments were performed to evaluate the biological role of PDLIM1 in GC cells. The Warburg effect was detected by a battery of glycolytic indicators. The interaction of PDLIM1 and hexokinase 2 (HK2) was determined by a co-immunoprecipitation assay. Furthermore, the modulatory effects of PDLIM1 and HK2 on Wnt/β-catenin signaling were assessed. The results showed that PDLIM1 expression was upregulated in GC tissues and cells and was associated with a poor prognosis for GC patients. PDLIM1 inhibition reduced GC cell proliferation, migration and invasion and promoted cell apoptosis. In the glucose deprivation (GLU-D) condition, the PDLIM1 level was reduced and PDLIM1 overexpression led to an increase in glycolysis. Besides, mechanistic investigation showed that PDLIM1 interacted with HK2 to mediate biological behaviors and the glycolysis of GC through Wnt/β-catenin signaling under glucose deprivation. In conclusion, PDLIM1 interacts with HK2 to promote gastric cancer progression by enhancing the Warburg effect via Wnt/β-catenin signaling.

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Authors and Affiliations

  1. Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital, NO. 1120, Lianhua Road, Futian District, Shenzhen, Guangdong, 518036, China

    Yunpeng Lei, Lirui He, Yue Li, Jianing Hou, Haoran Zhang & Guan Li

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  1. Yunpeng Lei
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  2. Lirui He
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  3. Yue Li
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  4. Jianing Hou
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  5. Haoran Zhang
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  6. Guan Li
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Contributions

Guan Li: Conceptualization, Writing- Reviewing and Editing. Yunpeng Lei: Data curation, Writing- Original draft preparation. Lirui He: Visualization, Investigation. Yue Li: Supervision. Jianing Hou: Methodology, Software. Haoran Zhang: Software, Validation.

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Correspondence to Guan Li.

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Ethics approval

This retrospective study was approved by the Ethics Committee of Peking University Shenzhen Hospital and conducted with the guide of the Declaration of Helsinki. All patients signed an informed consent form according to the standard process. All collected tissues were immediately refrigerated for subsequent experiments.

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The authors declare that they have no competing interests.

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Highlights

PDLIM1 expression was upregulated in GC tissues and cells, and was associated with poor prognosis of GC patients.

PDLIM1 inhibition inhibited GC cell proliferation, migration and invasion, and promoted cell apoptosis.

In the glucose deprivation condition, the PDLIM1 level was declined and PDLIM1 overexpression led to an increase in glycolysis.

PDLIM1 interacts with HK2 to promote gastric cancer progression through enhancing the Warburg effect via Wnt/β-catenin signaling.

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Lei, Y., He, L., Li, Y. et al. PDLIM1 interacts with HK2 to promote gastric cancer progression through enhancing the Warburg effect via Wnt/β-catenin signaling. Cell Tissue Res 395, 105–116 (2024). https://doi.org/10.1007/s00441-023-03840-z

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