LGALS1 is a protein belonging to the lectin family, widely distributed across immune and non-immune tissues. Characterized by high evolutionary conservation, LGALS1 specifically binds β-galactosides and functions as a multifunctional bioactive protein. It plays pivotal roles in immune regulation, cell migration, and tumor microenvironment remodeling. In malignant tumors, LGALS1 exhibits complex and context-dependent activities. This review systematically examines the downstream signaling pathways modulated by LGALS1—including NF-κB, PI3K/AKT/mTOR, MAPK, Hedgehog, TGF-β, and Wnt—highlighting its dual regulatory roles (promoting or inhibiting tumorigenesis) across cancer types. By synthesizing recent findings, we elucidate the molecular mechanisms underlying LGALS1’s context-specific effects and its influence on key signaling cascades. These insights aim to provide a theoretical framework and research directions for future studies targeting LGALS1 in cancer therapy.
References
[1]
Tuo, J.Y. and Xiang, Y.B. (2023) Research Progress on the Current Status of Cancer Epidemiology, Etiology, and Nutritional Epidemiology. Tumor, 43, 359-366.
[2]
Jiang, D., Wang, Z. and Liu, D.P. (2023) Current Prevalence and Distribution Characteristics of Malignant Tumors in China. Journal of Modern Urological and Genitourinary Oncology, 15, 374-375, 378.
[3]
Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249. https://doi.org/10.3322/caac.21660
[4]
Deo, S.V.S., Sharma, J. and Kumar, S. (2022) GLOBOCAN 2020 Report on Global Cancer Burden: Challenges and Opportunities for Surgical Oncologists. Annals of Surgical Oncology, 29, 6497-6500. https://doi.org/10.1245/s10434-022-12151-6
[5]
Wang, S.M. et al. (2024) Analysis of the Age Characteristics of Incidence and Mortality of Malignant Tumors in the Chinese Population in 2022. China Oncology, 33, 165-174.
[6]
Yip, H.Y.K. and Papa, A. (2021) Signaling Pathways in Cancer: Therapeutic Targets, Combinatorial Treatments, and New Developments. Cells, 10, Article 659. https://doi.org/10.3390/cells10030659
[7]
Astorgues-Xerri, L., Riveiro, M.E., Tijeras-Raballand, A., Serova, M., Neuzillet, C., Albert, S., et al. (2014) Unraveling Galectin-1 as a Novel Therapeutic Target for Cancer. Cancer Treatment Reviews, 40, 307-319. https://doi.org/10.1016/j.ctrv.2013.07.007
[8]
Cousin, J. and Cloninger, M. (2016) The Role of Galectin-1 in Cancer Progression, and Synthetic Multivalent Systems for the Study of Galectin-1. International Journal of Molecular Sciences, 17, Article 1566. https://doi.org/10.3390/ijms17091566
[9]
Camby, I., Le Mercier, M., Lefranc, F. and Kiss, R. (2006) Galectin-1: A Small Protein with Major Functions. Glycobiology, 16, 137R-157R. https://doi.org/10.1093/glycob/cwl025
[10]
Shi, Y., Tang, D., Li, X., Xie, X., Ye, Y. and Wang, L. (2022) Galectin Family Members: Emerging Novel Targets for Lymphoma Therapy? Frontiers in Oncology, 12, Article 889034. https://doi.org/10.3389/fonc.2022.889034
[11]
Qin, X.X., Sun, H.M., Zhao, H.P., Chu, W.H., Wang, D.T. and Li, C.Y. (2012) Galectin-1 Protein and Its Biological Functions. Chinese Journal of Animal Husbandry and Veterinary Medicine, 39, 141-145.
[12]
Bogut, A., Stojanovic, B., Jovanovic, M., Dimitrijevic Stojanovic, M., Gajovic, N., Stojanovic, B.S., et al. (2023) Galectin-1 in Pancreatic Ductal Adenocarcinoma: Bridging Tumor Biology, Immune Evasion, and Therapeutic Opportunities. International Journal of Molecular Sciences, 24, Article 15500. https://doi.org/10.3390/ijms242115500
[13]
Chen, W.B., et al. (2022) Galectin-1 Knockdown Inhibits Proliferation, Migration, Invasion and Promotes Apoptosis of Lung Adenocarcinoma Cells in Vitro. Journal of Southern Medical University, 42, 1628-1637.
[14]
You, X., Wu, J., Wang, Y., Liu, Q., Cheng, Z., Zhao, X., et al. (2020) Galectin-1 Promotes Vasculogenic Mimicry in Gastric Adenocarcinoma via the Hedgehog/GLI Signaling Pathway. Aging, 12, 21837-21853. https://doi.org/10.18632/aging.104000
[15]
Chong, Y., Tang, D., Xiong, Q., Jiang, X., Xu, C., Huang, Y., et al. (2016) Galectin-1 from Cancer-Associated Fibroblasts Induces Epithelial-Mesenchymal Transition through Β1 Integrin-Mediated Upregulation of Gli1 in Gastric Cancer. Journal of Experimental & Clinical Cancer Research, 35, Article No. 175. https://doi.org/10.1186/s13046-016-0449-1
[16]
Chong, Y. (2017) The Role of Galectin-1 in the Invasion and Metastasis of Gastric Adenocarcinoma and the Effect of Dihydroartemisinin on Its Expression. Master’s Thesis, Yangzhou University.
[17]
Bai, Y., Wang, Y.X., Yao, W.J. and Wang, Z.M. (2013) Effects of Downregulation of Galectin-1 Expression on the Proliferation of Esophageal Squamous Cell Carcinoma Cells. Chinese Journal of Gerontology, 33, 365-366.
[18]
Chetry, M., Song, Y., Pan, C., Li, R., Zhang, J. and Zhu, X. (2020) Effects of Galectin-1 on Biological Behavior in Cervical Cancer. Journal of Cancer, 11, 1584-1595. https://doi.org/10.7150/jca.38538
[19]
Wu, L.X., et al. (2018) Expression of Galectin-1 in Bladder Cancer Cells and Its Effect on the Proliferation and Migration Abilities of Bladder Cancer Cells. Chinese Journal of Medical Engineering, 26, 6-11.
[20]
Chou, F., Chen, H., Kuo, C. and Sytwu, H. (2018) Role of Galectins in Tumors and in Clinical Immunotherapy. International Journal of Molecular Sciences, 19, Article 430. https://doi.org/10.3390/ijms19020430
[21]
Huang, Y., Wang, H., Zhao, J., Wu, M. and Shih, T. (2021) Immunosuppressive Roles of Galectin-1 in the Tumor Microenvironment. Biomolecules, 11, Article 1398. https://doi.org/10.3390/biom11101398
[22]
Zhou, Y., Cui, C., Ma, X., Luo, W., Zheng, S.G. and Qiu, W. (2020) Nuclear Factor κB (NF-κB)-Mediated Inflammation in Multiple Sclerosis. Frontiers in Immunology, 11, Artice 391. https://doi.org/10.3389/fimmu.2020.00391
[23]
Cui, Y., Yan, M., Wu, W., Lv, P., Wang, J., Huo, Y., et al. (2022) ESCCAL-1 Promotes Cell-Cycle Progression by Interacting with and Stabilizing Galectin-1 in Esophageal Squamous Cell Carcinoma. NPJ Precision Oncology, 6, Article No. 12. https://doi.org/10.1038/s41698-022-00255-x
[24]
Satelli, A. and Rao, U.S. (2011) Galectin-1 Is Silenced by Promoter Hypermethylation and Its Re-Expression Induces Apoptosis in Human Colorectal Cancer Cells. Cancer Letters, 301, 38-46. https://doi.org/10.1016/j.canlet.2010.10.027
[25]
Bacigalupo, M.L., Carabias, P. and Troncoso, M.F. (2017) Contribution of Galectin-1, a Glycan-Binding Protein, to Gastrointestinal Tumor Progression. World Journal of Gastroenterology, 23, 5266-5281. https://doi.org/10.3748/wjg.v23.i29.5266
[26]
Su, Y., Luo, H., Huang, C., Liu, T., Huang, E., Sung, M., et al. (2020) Galectin-1 Overexpression Activates the FAK/PI3K/AKT/mTOR Pathway and Is Correlated with Upper Urinary Urothelial Carcinoma Progression and Survival. Cells, 9, Article 806. https://doi.org/10.3390/cells9040806
[27]
Shi, R., Mo, H.L., Li, Y.B., Zhang, Z.B. and Li, H. (2023) The Role and Mechanism of Galectin-1 in the Inhibition of Cholangiocarcinoma Cell Proliferation by Metformin. Journal of Hunan Normal University (Medical Edition), 20, 18-23.
[28]
Li, J., Tseng, C., Lin, C., Law, C., Chien, Y., Kuo, W., et al. (2018) Upregulation of LGALS1 Is Associated with Oral Cancer Metastasis. Therapeutic Advances in Medical Oncology, 10, 1-20. https://doi.org/10.1177/1758835918794622
[29]
Miao, J., Wang, S., Zhang, M., Yu, F., Zhang, L., Yu, Z., et al. (2014) Knockdown of Galectin-1 Suppresses the Growth and Invasion of Osteosarcoma Cells through Inhibition of the MAPK/ERK Pathway. Oncology Reports, 32, 1497-1504. https://doi.org/10.3892/or.2014.3358
[30]
Zhu, J., Zheng, Y., Zhang, H., Liu, Y., Sun, H. and Zhang, P. (2019) Galectin-1 Induces Metastasis and Epithelial-Mesenchymal Transition (EMT) in Human Ovarian Cancer Cells via Activation of the MAPK JNK/p38 Signalling Pathway. American Journal of Translational Research, 11, 3862-3878.
[31]
Deng, X.Y., Lin, H.Y. and Chen, W.G. (2018) Expression of Galectin-1 and VEGF in Cervical Squamous Cell Carcinoma and Their Relationship with Clinical Characteristics. Cancer Progress, 16, 1278-1280.
[32]
Peng, K., Jiang, S., Lee, Y., Tsai, F., Chang, C., Chen, L., et al. (2021) Stromal Galectin-1 Promotes Colorectal Cancer Cancer-Initiating Cell Features and Disease Dissemination through SOX9 and β-Catenin: Development of Niche-Based Biomarkers. Frontiers in Oncology, 11, Article 716055. https://doi.org/10.3389/fonc.2021.716055
[33]
Martínez-Bosch, N., Fernández-Barrena, M.G., Moreno, M., Ortiz-Zapater, E., Munné-Collado, J., Iglesias, M., et al. (2014) Galectin-1 Drives Pancreatic Carcinogenesis through Stroma Remodeling and Hedgehog Signaling Activation. Cancer Research, 74, 3512-3524. https://doi.org/10.1158/0008-5472.can-13-3013
[34]
You, X., Wu, J., Zhao, X., Jiang, X., Tao, W., Chen, Z., et al. (2021) Fibroblastic Galectin-1-Fostered Invasion and Metastasis Are Mediated by TGF-β1-Induced Epithelial-Mesenchymal Transition in Gastric Cancer. Aging, 13, 18464-18481. https://doi.org/10.18632/aging.203295
[35]
Zhu, X., Wang, K., Zhang, K., Xu, F., Yin, Y., Zhu, L., et al. (2016) Galectin-1 Knockdown in Carcinoma-Associated Fibroblasts Inhibits Migration and Invasion of Human MDA-MB-231 Breast Cancer Cells by Modulating MMP-9 Expression. Acta Biochimica et Biophysica Sinica, 48, 462-467. https://doi.org/10.1093/abbs/gmw019
[36]
Kizilirmak, C., Bianchi, M.E. and Zambrano, S. (2022) Insights on the NF-κB System Using Live Cell Imaging: Recent Developments and Future Perspectives. Frontiers in Immunology, 13, Article 886127. https://doi.org/10.3389/fimmu.2022.886127
[37]
Cornice, J., Verzella, D., Arboretto, P., Vecchiotti, D., Capece, D., Zazzeroni, F., et al. (2024) NF-κB: Governing Macrophages in Cancer. Genes, 15, Article 197. https://doi.org/10.3390/genes15020197
[38]
Choi, M., Jo, J., Park, J., Kang, H.K. and Park, Y. (2019) NF-κB Signaling Pathways in Osteoarthritic Cartilage Destruction. Cells, 8, Article 734. https://doi.org/10.3390/cells8070734
[39]
Schrank, T.P., et al. (2022) NF-κB Over-Activation Portends Improved Outcomes in HPV-Associated Head and Neck Cancer. Oncotarget, 13, 707-722.
[40]
Barnabei, L., Laplantine, E., Mbongo, W., Rieux-Laucat, F. and Weil, R. (2021) Nf-κB: At the Borders of Autoimmunity and Inflammation. Frontiers in Immunology, 12, Article 716469. https://doi.org/10.3389/fimmu.2021.716469
[41]
Martin, M., Sun, M., Motolani, A. and Lu, T. (2021) The Pivotal Player: Components of NF-κB Pathway as Promising Biomarkers in Colorectal Cancer. International Journal of Molecular Sciences, 22, Article 7429. https://doi.org/10.3390/ijms22147429
[42]
Deka, K. and Li, Y. (2023) Transcriptional Regulation during Aberrant Activation of NF-κB Signalling in Cancer. Cells, 12, Article 788. https://doi.org/10.3390/cells12050788
[43]
Miricescu, D., Totan, A., Stanescu-Spinu, I., Badoiu, S.C., Stefani, C. and Greabu, M. (2020) PI3K/AKT/mTOR Signaling Pathway in Breast Cancer: From Molecular Landscape to Clinical Aspects. International Journal of Molecular Sciences, 22, Article 173. https://doi.org/10.3390/ijms22010173
[44]
Aguayo, F., Perez-Dominguez, F., Osorio, J.C., Oliva, C. and Calaf, G.M. (2023) PI3K/AKT/mTOR Signaling Pathway in HPV-Driven Head and Neck Carcinogenesis: Therapeutic Implications. Biology, 12, Article 672. https://doi.org/10.3390/biology12050672
[45]
Luo, Q., Du, R., Liu, W., Huang, G., Dong, Z. and Li, X. (2022) PI3K/AKT/mTOR Signaling Pathway: Role in Esophageal Squamous Cell Carcinoma, Regulatory Mechanisms and Opportunities for Targeted Therapy. Frontiers in Oncology, 12, Article 852383. https://doi.org/10.3389/fonc.2022.852383
[46]
Li, W.S., Wang, T.T. and He, W.Q. (2024) Relationship between the PI3K/Akt/mTOR Signaling Pathway and Autophagy Regulation and Related Diseases. Chongqing Medicine, 53, 2047-2052.
[47]
Dai, Y.Z., Li, Y.N. and Shang, R.Z. (2024) Research Progress on the Mechanism of Action of the PI3K/AKT/mTOR Signaling Pathway in Liver Cancer. Journal of Hepatobiliary and Pancreatic Surgery, 36, 116-123.
[48]
Yang, G.N. and Zhang, X.P. (2024) Research Progress on the PI3K/AKT/mTOR Signaling Pathway in Targeted Therapy for Triple-Negative Breast Cancer. Chinese Medical Innovation, 21, 155-158.
[49]
Kyosseva, S.V. (2016) Targeting MAPK Signaling in Age-Related Macular Degeneration. Ophthalmology and Eye Diseases, 8, 23-30. https://doi.org/10.4137/oed.s32200
[50]
Kurtzeborn, K., Kwon, H.N. and Kuure, S. (2019) MAPK/ERK Signaling in Regulation of Renal Differentiation. International Journal of Molecular Sciences, 20, Article 1779. https://doi.org/10.3390/ijms20071779
[51]
Guo, Y., Pan, W., Liu, S., Shen, Z., Xu, Y. and Hu, L. (2020) ERK/MAPK Signalling Pathway and Tumorigenesis (Review). Experimental and Therapeutic Medicine, 19, 1997-2007. https://doi.org/10.3892/etm.2020.8454
[52]
Colozza, G. and Koo, B. (2021) Wnt/β‐Catenin Signaling: Structure, Assembly and Endocytosis of the Signalosome. Development, Growth & Differentiation, 63, 199-218. https://doi.org/10.1111/dgd.12718
[53]
Liu, J., Xiao, Q., Xiao, J., Niu, C., Li, Y., Zhang, X., et al. (2022) Wnt/β-Catenin Signaling: Function, Biological Mechanisms, and Therapeutic Opportunities. Signal Transduction and Targeted Therapy, 7, Article No. 3. https://doi.org/10.1038/s41392-021-00762-6
[54]
Yu, F., Yu, C., Li, F., Zuo, Y., Wang, Y., Yao, L., et al. (2021) Wnt/β-Catenin Signaling in Cancers and Targeted Therapies. Signal Transduction and Targeted Therapy, 6, Article No. 307. https://doi.org/10.1038/s41392-021-00701-5
[55]
Skoda, A.M., Simovic, D., Karin, V., Kardum, V., Vranic, S. and Serman, L. (2018) The Role of the Hedgehog Signaling Pathway in Cancer: A Comprehensive Review. Bosnian Journal of Basic Medical Sciences, 18, 8-20. https://doi.org/10.17305/bjbms.2018.2756
[56]
Gao, L., Zhang, Z., Zhang, P., Yu, M. and Yang, T. (2018) Role of Canonical Hedgehog Signaling Pathway in Liver. International Journal of Biological Sciences, 14, 1636-1644. https://doi.org/10.7150/ijbs.28089
[57]
Cellière, G., Fengos, G., Hervé, M. and Iber, D. (2011) The Plasticity of TGF-β Signaling. BMC Systems Biology, 5, Article No. 184. https://doi.org/10.1186/1752-0509-5-184
[58]
Morikawa, M., Derynck, R. and Miyazono, K. (2016) TGF-β and the TGF-β Family: Context-Dependent Roles in Cell and Tissue Physiology. Cold Spring Harbor Perspectives in Biology, 8, a021873. https://doi.org/10.1101/cshperspect.a021873
