HIF-1α Mediated Regulation of Glioblastoma Malignant Phenotypes Through CD47 Protein: Understanding Functions and Mechanisms

Overview

Journal J Cancer

Date 2025 Jan 9

PMID 39781344

Authors

Qijia Tan

Feng Li

Jun Wang

Yuxi Zou

Yanping Tang

Yingqian Cai

Xiaodan Jiang

Affiliations

Soon will be listed here.

Abstract

Glioblastoma (GBM) is a highly invasive and malignant primary intracranial tumor originating from glial cells, and it is associated with an extremely poor clinical prognosis. The hypoxic conditions within GBM promote various tumor cell processes such as angiogenesis, proliferation, migration, invasion, and drug resistance. A key aspect of tumor adaptation to the hypoxic environment and the promotion of malignant behaviors is the regulation of HIF-1α signaling pathways. However, the specific pathogenic mechanisms involving HIF-1α in GBM have not been thoroughly investigated. This study reveals significant overexpression of both HIF-1α and CD47 in GBM. Patients with high HIF-1α levels and CD47 expression had significantly reduced overall survival and disease-free survival times. Furthermore, a positive correlation was observed between the expression levels of HIF-1α and CD47 in GBM. Lentivirus-mediated knockdown of HIF-1α protein and plasmid-based overexpression of CD47 protein simultaneously enhanced cell proliferation, clonogenic potential and cell migration abilities in GBM, and HIF-1α was found to regulate key pathways, including the P-PI3K/P-AKT, SOX2/OCT4 and MMP2/MMP9 pathways, in GBM.

References

Noorolyai S, Shajari N, Baghbani E, Sadreddini S, Baradaran B . The relation between PI3K/AKT signalling pathway and cancer. Gene. 2019; 698:120-128. DOI: 10.1016/j.gene.2019.02.076. View

Bi Y, Min M, Shen W, Liu Y . Genistein induced anticancer effects on pancreatic cancer cell lines involves mitochondrial apoptosis, G/Gcell cycle arrest and regulation of STAT3 signalling pathway. Phytomedicine. 2018; 39:10-16. DOI: 10.1016/j.phymed.2017.12.001. View

Verma P, Shukla N, Kumari S, Ansari M, Gautam N, Patel G . Cancer stem cell in prostate cancer progression, metastasis and therapy resistance. Biochim Biophys Acta Rev Cancer. 2023; 1878(3):188887. DOI: 10.1016/j.bbcan.2023.188887. View

Cui X, Tan Morales R, Qian W, Wang H, Gagner J, Dolgalev I . Hacking macrophage-associated immunosuppression for regulating glioblastoma angiogenesis. Biomaterials. 2018; 161:164-178. PMC: 8059366. DOI: 10.1016/j.biomaterials.2018.01.053. View

Yang K, Wu Z, Zhang H, Zhang N, Wu W, Wang Z . Glioma targeted therapy: insight into future of molecular approaches. Mol Cancer. 2022; 21(1):39. PMC: 8822752. DOI: 10.1186/s12943-022-01513-z. View

Akbarzadeh M, Mihanfar A, Akbarzadeh S, Yousefi B, Majidinia M . Crosstalk between miRNA and PI3K/AKT/mTOR signaling pathway in cancer. Life Sci. 2021; 285:119984. DOI: 10.1016/j.lfs.2021.119984. View

Chebbi I, Migianu-Griffoni E, Sainte-Catherine O, Lecouvey M, Seksek O . In vitro assessment of liposomal neridronate on MDA-MB-231 human breast cancer cells. Int J Pharm. 2009; 383(1-2):116-22. DOI: 10.1016/j.ijpharm.2009.09.011. View

Kwok W, Man Ho J, Tam T, Ip M, Lam D . Survival benefits from afatinib compared with gefitinib and erlotinib among patients with common EGFR mutation in first-line setting. Thorac Cancer. 2022; 13(14):2057-2063. PMC: 9284183. DOI: 10.1111/1759-7714.14528. View

Liu J, Chen T, Li S, Liu W, Wang P, Shang G . Targeting matrix metalloproteinases by E3 ubiquitin ligases as a way to regulate the tumor microenvironment for cancer therapy. Semin Cancer Biol. 2022; 86(Pt 2):259-268. DOI: 10.1016/j.semcancer.2022.06.004. View

10.

Cloughesy T, Cavenee W, Mischel P . Glioblastoma: from molecular pathology to targeted treatment. Annu Rev Pathol. 2013; 9:1-25. DOI: 10.1146/annurev-pathol-011110-130324. View

11.

Liu Y, Wang Y, Yang Y, Weng L, Wu Q, Zhang J . Emerging phagocytosis checkpoints in cancer immunotherapy. Signal Transduct Target Ther. 2023; 8(1):104. PMC: 9990587. DOI: 10.1038/s41392-023-01365-z. View

12.

Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z . GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017; 45(W1):W98-W102. PMC: 5570223. DOI: 10.1093/nar/gkx247. View

13.

Zhao M, Luo R, Liu Y, Gao L, Fu Z, Fu Q . miR-3188 regulates nasopharyngeal carcinoma proliferation and chemosensitivity through a FOXO1-modulated positive feedback loop with mTOR-p-PI3K/AKT-c-JUN. Nat Commun. 2016; 7:11309. PMC: 4842991. DOI: 10.1038/ncomms11309. View

14.

Jiang Y, Qian Y, Hong H, Gao X, Liu W, Jin Q . Morin protects chicks with T-2 toxin poisoning by decreasing heterophil extracellular traps, oxidative stress and inflammatory response. Br Poult Sci. 2023; 64(5):614-624. DOI: 10.1080/00071668.2023.2226083. View

15.

Cowman S, Koh M . Revisiting the HIF switch in the tumor and its immune microenvironment. Trends Cancer. 2021; 8(1):28-42. PMC: 8702465. DOI: 10.1016/j.trecan.2021.10.004. View

16.

Yu L, Wei J, Liu P . Attacking the PI3K/Akt/mTOR signaling pathway for targeted therapeutic treatment in human cancer. Semin Cancer Biol. 2021; 85:69-94. DOI: 10.1016/j.semcancer.2021.06.019. View

17.

Hoang-Minh L, Mitchell D . Immunotherapy for Brain Tumors. Curr Treat Options Oncol. 2018; 19(11):60. DOI: 10.1007/s11864-018-0576-3. View

18.

Kawakita E, Yang F, Shi S, Takagaki Y, Koya D, Kanasaki K . Inhibition of Dipeptidyl Peptidase-4 Activates Autophagy to Promote Survival of Breast Cancer Cells via the mTOR/HIF-1α Pathway. Cancers (Basel). 2023; 15(18). PMC: 10526496. DOI: 10.3390/cancers15184529. View

19.

Gabriely G, Wheeler M, Takenaka M, Quintana F . Role of AHR and HIF-1α in Glioblastoma Metabolism. Trends Endocrinol Metab. 2017; 28(6):428-436. PMC: 5438779. DOI: 10.1016/j.tem.2017.02.009. View

20.

Bian H, Shen Y, Zhou Y, Nagle D, Guan Y, Zhang W . CD47: Beyond an immune checkpoint in cancer treatment. Biochim Biophys Acta Rev Cancer. 2022; 1877(5):188771. DOI: 10.1016/j.bbcan.2022.188771. View