Journal of Gastric Cancer

  • 제24권3호
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  • Pages.300-315
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  • 2024
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  • 2093-582X(pISSN)
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  • 2093-5641(eISSN)
대한위암학회 (The Korean Gastric Cancer Association)
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Galectin-1 Promotes Gastric Carcinoma Progression and Cisplatin Resistance Through the NRP-1/c-JUN/Wee1 Pathway

  • Zhengyang Pan (Department of Gastrointestinal Surgery, Zhejiang Chinese Medical University) ;
  • Guoxi Xu (Department of Gastrointestinal Surgery, Jinjiang Hospital) ;
  • Yan Zhang (Cancer Center, Department of Genetic and Genomic Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College) ;
  • Meiling Wu (General Surgery, Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College) ;
  • Jiahui Yu (Cancer Center, Department of Genetic and Genomic Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College) ;
  • Xujun He (Cancer Center, Department of Genetic and Genomic Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College) ;
  • Wei Zhang (Department of Gastrointestinal Surgery, Zhejiang Chinese Medical University) ;
  • Junfeng Hu (General Surgery, Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College)
  • 투고 : 2023.12.04
  • 심사 : 2024.05.14
  • 발행 : 2024.07.01
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초록

Purpose: Gastric cancer (GC) is among the deadliest malignancies and the third leading cause of cancer-related deaths worldwide. Galectin-1 (Gal-1) is a primary protein secreted by cancer-associated fibroblasts (CAFs); however, its role and mechanisms of action of Gal-1 in GC remain unclear. In this study, we stimulated GC cells with exogenous human recombinant galectin-1 protein (rhGal-1) to investigate its effects on the proliferation, migration, and resistance to cisplatin. Materials and Methods: We used simulated rhGal-1 protein as a paracrine factor produced by CAFs to induce GC cells and investigated its promotional effects and mechanisms in GC progression and cisplatin resistance. Immunohistochemical (IHC) assay confirmed that Gal-1 expression was associated with clinicopathological parameters and correlated with the expression of neuropilin-1 (NRP-1), c-JUN, and Wee1. Results: Our study reveals Gal-1 expression was significantly associated with poor outcomes. Gal-1 boosts the proliferation and metastasis of GC cells by activating the NRP-1/C-JUN/Wee1 pathway. Gal-1 notably increases GC cell resistance to cisplatin The NRP-1 inhibitor, EG00229, effectively counteracts these effects. Conclusions: These findings revealed a potential mechanism by which Gal-1 promotes GC growth and contributes to chemoresistance, offering new therapeutic targets for the treatment of GC.

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과제정보

This work was supported by grants from the Zhejiang Provincial Natural Science Foundation (LY22H160039), the Medicine and Health Research Foundation of Zhejiang Province (2021KY446 and 2022KY023), the Zhejiang Traditional Chinese Medicine Science and Technology Plan (2021ZB022 and 2021ZA005), and the Zhejiang Health Commission Fund project (2021PY035).

참고문헌

  1. Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. Lancet 2020;396:635-648.
  2. Wu F, Yang J, Liu J, Wang Y, Mu J, Zeng Q, et al. Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer. Signal Transduct Target Ther 2021;6:218.
  3. Saw PE, Chen J, Song E. Targeting CAFs to overcome anticancer therapeutic resistance. Trends Cancer 2022;8:527-555.
  4. Zhang H, Zhang X, Wu X, Li W, Su P, Cheng H, et al. Interference of Frizzled 1 (FZD1) reverses multidrug resistance in breast cancer cells through the Wnt/β-catenin pathway. Cancer Lett 2012;323:106-113.
  5. Zhang Q, Ali M, Wang Y, Sun QN, Zhu XD, Tang D, et al. Galectin-1 binds GRP78 to promote the proliferation and metastasis of gastric cancer. Int J Oncol 2022;61:141.
  6. Tsai YT, Li CY, Huang YH, Chang TS, Lin CY, Chuang CH, et al. Galectin-1 orchestrates an inflammatory tumor-stroma crosstalk in hepatoma by enhancing TNFR1 protein stability and signaling in carcinoma-associated fibroblasts. Oncogene 2022;41:3011-3023.
  7. Wu MH, Chen YL, Lee KH, Chang CC, Cheng TM, Wu SY, et al. Glycosylation-dependent galectin-1/neuropilin-1 interactions promote liver fibrosis through activation of TGF-β- and PDGF-like signals in hepatic stellate cells. Sci Rep 2017;7:11006.
  8. You X, Wu J, Zhao X, Jiang X, Tao W, Chen Z, et al. Fibroblastic galectin-1-fostered invasion and metastasis are mediated by TGF-β1-induced epithelial-mesenchymal transition in gastric cancer. Aging (Albany NY) 2021;13:18464-18481.
  9. Paz A, Haklai R, Elad-Sfadia G, Ballan E, Kloog Y. Galectin-1 binds oncogenic H-Ras to mediate Ras membrane anchorage and cell transformation. Oncogene 2001;20:7486-7493.
  10. Vyakarnam A, Dagher SF, Wang JL, Patterson RJ. Evidence for a role for galectin-1 in pre-mRNA splicing. Mol Cell Biol 1997;17:4730-4737.
  11. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019;69:7-34.
  12. Shi ZD, Hao L, Han XX, Wu ZX, Pang K, Dong Y, et al. Targeting HNRNPU to overcome cisplatin resistance in bladder cancer. Mol Cancer 2022;21:37.
  13. MacDonagh L, Gray SG, Breen E, Cuffe S, Finn SP, O'Byrne KJ, et al. BBI608 inhibits cancer stemness and reverses cisplatin resistance in NSCLC. Cancer Lett 2018;428:117-126.
  14. Hu P, So K, Chen H, Lin Q, Xu M, Lin Y. A monoclonal antibody against basic fibroblast growth factor attenuates cisplatin resistance in lung cancer by suppressing the epithelial-mesenchymal transition. Int J Immunopathol Pharmacol 2022;36:3946320221105134.
  15. Kuo KL, Liu SH, Lin WC, Hsu FS, Chow PM, Chang YW, et al. Trifluoperazine, an antipsychotic drug, effectively reduces drug resistance in cisplatin-resistant urothelial carcinoma cells via suppressing Bcl-xL: an in vitro and in vivo study. Int J Mol Sci 2019;20:3218.
  16. Zhu M, Zhang P, Yu S, Tang C, Wang Y, Shen Z, et al. Targeting ZFP64/GAL-1 axis promotes therapeutic effect of nab-paclitaxel and reverses immunosuppressive microenvironment in gastric cancer. J Exp Clin Cancer Res 2022;41:14.
  17. Shen H, He T, Wang S, Hou L, Wei Y, Liu Y, et al. SOX4 promotes beige adipocyte-mediated adaptive thermogenesis by facilitating PRDM16-PPARγ complex. Theranostics 2022;12:7699-7716.
  18. Rizzolio S, Corso S, Giordano S, Tamagnone L. Autocrine signaling of NRP1 ligand galectin-1 elicits resistance to BRAF-targeted therapy in melanoma cells. Cancers (Basel) 2020;12:2218.
  19. Zhu P, Liu G, Wang X, Lu J, Zhou Y, Chen S, et al. Transcription factor c-Jun modulates GLUT1 in glycolysis and breast cancer metastasis. BMC Cancer 2022;22:1283.
  20. Li J, Pan C, Boese AC, Kang J, Umano AD, Magliocca KR, et al. DGKA provides platinum resistance in ovarian cancer through activation of c-JUN-WEE1 signaling. Clin Cancer Res 2020;26:3843-3855.
  21. de Visser KE, Joyce JA. The evolving tumor microenvironment: from cancer initiation to metastatic outgrowth. Cancer Cell 2023;41:374-403.
  22. Su S, Chen J, Yao H, Liu J, Yu S, Lao L, et al. CD10+GPR77+ cancer-associated fibroblasts promote cancer formation and chemoresistance by sustaining cancer stemness. Cell 2018;172:841-856.e16.
  23. Auciello FR, Bulusu V, Oon C, Tait-Mulder J, Berry M, Bhattacharyya S, et al. A stromal lysolipid-autotaxin signaling axis promotes pancreatic tumor progression. Cancer Discov 2019;9:617-627.
  24. Calon A, Espinet E, Palomo-Ponce S, Tauriello DV, Iglesias M, Cespedes MV, et al. Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation. Cancer Cell 2012;22:571-584.
  25. Zhang Z, Liang Z, Li D, Wang L, Chen Y, Liang Y, et al. Development of a CAFs-related gene signature to predict survival and drug response in bladder cancer. Hum Cell 2022;35:649-664.
  26. Wu MH, Hong HC, Hong TM, Chiang WF, Jin YT, Chen YL. Targeting galectin-1 in carcinoma-associated fibroblasts inhibits oral squamous cell carcinoma metastasis by downregulating MCP-1/CCL2 expression. Clin Cancer Res 2011;17:1306-1316.
  27. Leung Z, Ko FC, Tey SK, Kwong EM, Mao X, Liu BH, et al. Galectin-1 promotes hepatocellular carcinoma and the combined therapeutic effect of OTX008 galectin-1 inhibitor and sorafenib in tumor cells. J Exp Clin Cancer Res 2019;38:423.
  28. Wu MH, Ying NW, Hong TM, Chiang WF, Lin YT, Chen YL. Galectin-1 induces vascular permeability through the neuropilin-1/vascular endothelial growth factor receptor-1 complex. Angiogenesis 2014;17:839-849.
  29. Papavassiliou AG, Musti AM. The multifaceted output of c-Jun biological activity: focus at the junction of CD8 T cell activation and exhaustion. Cells 2020;9:2470.
  30. Ghelli Luserna di Rora A, Cerchione C, Martinelli G, Simonetti G. A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target. J Hematol Oncol 2020;13:126.