Progranulin and Its Biological Effects in Cancer

Overview

Journal Med Oncol

Publisher Springer

Specialty Oncology

Date 2017 Nov 9

PMID 29116422

Citations 53

Authors

Fabian Arechavaleta-Velasco

Carlos Eduardo Perez-Juarez

George L Gerton

Laura Diaz-Cueto

Affiliations

Soon will be listed here.

Abstract

Cancer cells have defects in regulatory mechanisms that usually control cell proliferation and homeostasis. Different cancer cells share crucial alterations in cell physiology, which lead to malignant growth. Tumorigenesis or tumor growth requires a series of events that include constant cell proliferation, promotion of metastasis and invasion, stimulation of angiogenesis, evasion of tumor suppressor factors, and avoidance of cell death pathways. All these events in tumor progression may be regulated by growth factors produced by normal or malignant cells. The growth factor progranulin has significant biological effects in different types of cancer. This protein is a regulator of tumorigenesis because it stimulates cell proliferation, migration, invasion, angiogenesis, malignant transformation, resistance to anticancer drugs, and immune evasion. This review focuses on the biological effects of progranulin in several cancer models and provides evidence that this growth factor should be considered as a potential biomarker and target in cancer treatment.

Citing Articles

Tumor Cell Survival Factors and Angiogenesis in Chronic Lymphocytic Leukemia: How Hot Is the Link?.

Ayoub M, Susin S, Bauvois B Cancers (Basel). 2025; 17(1.

PMID: 39796700 PMC: 11719013. DOI: 10.3390/cancers17010072.

Plasma levels of progranulin, a tumorigenic protein, are persistently elevated during the first month after minimally invasive colorectal cancer resection.

Shantha Kumara H, Hedjar Y, Mitra N, Miyagaki H, Yan X, Cekic V J Gastrointest Oncol. 2024; 15(5):2157-2165.

PMID: 39554587 PMC: 11565126. DOI: 10.21037/jgo-24-114.

Blood-Based Biomarkers in Frontotemporal Dementia: A Narrative Review.

Liampas I, Kyriakoulopoulou P, Karakoida V, Kavvoura P, Sgantzos M, Bogdanos D Int J Mol Sci. 2024; 25(21).

PMID: 39519389 PMC: 11546606. DOI: 10.3390/ijms252111838.

Novel T cell exhaustion gene signature to predict prognosis and immunotherapy response in thyroid carcinoma from integrated RNA-sequencing analysis.

Li Y, Wang Z, Lu F, Miao Y, Feng Q, Zhu W Sci Rep. 2024; 14(1):8375.

PMID: 38600248 PMC: 11006682. DOI: 10.1038/s41598-024-58419-7.

Progranulin Facilitates Corneal Repair Through Dual Mechanisms of Inflammation Suppression and Regeneration Promotion.

Yan D, Zhang Y, Huang Y, Ouyang W Inflammation. 2024; 47(5):1648-1666.

PMID: 38460093 DOI: 10.1007/s10753-024-01999-3.

References

Feng J, Guo F, Jiang B, Zhang Y, Frenkel S, Wang D . Granulin epithelin precursor: a bone morphogenic protein 2-inducible growth factor that activates Erk1/2 signaling and JunB transcription factor in chondrogenesis. FASEB J. 2010; 24(6):1879-92. PMC: 2874481. DOI: 10.1096/fj.09-144659. View

Soukup V, Kalousova M, Capoun O, Sobotka R, Breyl Z, Pesl M . Panel of Urinary Diagnostic Markers for Non-Invasive Detection of Primary and Recurrent Urothelial Urinary Bladder Carcinoma. Urol Int. 2015; 95(1):56-64. DOI: 10.1159/000368166. View

Salazar D, Butler V, Argouarch A, Hsu T, Mason A, Nakamura A . The Progranulin Cleavage Products, Granulins, Exacerbate TDP-43 Toxicity and Increase TDP-43 Levels. J Neurosci. 2015; 35(25):9315-28. PMC: 4478251. DOI: 10.1523/JNEUROSCI.4808-14.2015. View

Edelman M, Feliciano J, Yue B, Bejarano P, Ioffe O, Reisman D . GP88 (progranulin): a novel tissue and circulating biomarker for non-small cell lung carcinoma. Hum Pathol. 2014; 45(9):1893-9. PMC: 4150823. DOI: 10.1016/j.humpath.2014.05.011. View

Butler G, Dean R, Tam E, Overall C . Pharmacoproteomics of a metalloproteinase hydroxamate inhibitor in breast cancer cells: dynamics of membrane type 1 matrix metalloproteinase-mediated membrane protein shedding. Mol Cell Biol. 2008; 28(15):4896-914. PMC: 2493375. DOI: 10.1128/MCB.01775-07. View

Chen X, Li J, Liang Q, He D, Zhao J . Expression of PC cell-derived growth factor and vascular endothelial growth factor in esophageal squamous cell carcinoma and their clinicopathologic significance. Chin Med J (Engl). 2008; 121(10):881-6. View

Lu Y, Zheng L, Zhang W, Feng T, Liu J, Wang X . Growth factor progranulin contributes to cervical cancer cell proliferation and transformation in vivo and in vitro. Gynecol Oncol. 2014; 134(2):364-71. DOI: 10.1016/j.ygyno.2014.05.025. View

Toh H, Chitramuthu B, Bennett H, Bateman A . Structure, function, and mechanism of progranulin; the brain and beyond. J Mol Neurosci. 2011; 45(3):538-48. DOI: 10.1007/s12031-011-9569-4. View

Baba T, Hoff 3rd H, Nemoto H, Lee H, Orth J, Arai Y . Acrogranin, an acrosomal cysteine-rich glycoprotein, is the precursor of the growth-modulating peptides, granulins, and epithelins, and is expressed in somatic as well as male germ cells. Mol Reprod Dev. 1993; 34(3):233-43. DOI: 10.1002/mrd.1080340302. View

10.

Wang M, Li G, Yin J, Lin T, Zhang J . Progranulin overexpression predicts overall survival in patients with glioblastoma. Med Oncol. 2011; 29(4):2423-31. DOI: 10.1007/s12032-011-0131-6. View

11.

Bhandari V, Bateman A . Structure and chromosomal location of the human granulin gene. Biochem Biophys Res Commun. 1992; 188(1):57-63. DOI: 10.1016/0006-291x(92)92349-3. View

12.

Wang W, Hayashi J, Serrero G . PC cell-derived growth factor confers resistance to dexamethasone and promotes tumorigenesis in human multiple myeloma. Clin Cancer Res. 2006; 12(1):49-56. DOI: 10.1158/1078-0432.CCR-05-0929. View

13.

Diaz-Cueto L, Stein P, Jacobs A, Schultz R, Gerton G . Modulation of mouse preimplantation embryo development by acrogranin (epithelin/granulin precursor). Dev Biol. 2000; 217(2):406-18. DOI: 10.1006/dbio.1999.9564. View

14.

Selmy M, Ibrahim G, El Serafi T, Ghobeish A . Evaluation of urinary proepithelin as a potential biomarker for bladder cancer detection and prognosis in Egyptian patients. Cancer Biomark. 2011; 7(3):163-70. DOI: 10.3233/CBM-2010-0186. View

15.

Nicholson A, Finch N, Rademakers R . Human genetics as a tool to identify progranulin regulators. J Mol Neurosci. 2011; 45(3):532-7. PMC: 3310391. DOI: 10.1007/s12031-011-9554-y. View

16.

Cheung P, Cheng C, Wong N, Ho J, Yip C, Lui V . Granulin-epithelin precursor is an oncofetal protein defining hepatic cancer stem cells. PLoS One. 2011; 6(12):e28246. PMC: 3241621. DOI: 10.1371/journal.pone.0028246. View

17.

Feng T, Zheng L, Liu F, Xu X, Mao S, Wang X . Growth factor progranulin promotes tumorigenesis of cervical cancer via PI3K/Akt/mTOR signaling pathway. Oncotarget. 2016; 7(36):58381-58395. PMC: 5295437. DOI: 10.18632/oncotarget.11126. View

18.

He Z, Bateman A . Progranulin gene expression regulates epithelial cell growth and promotes tumor growth in vivo. Cancer Res. 1999; 59(13):3222-9. View

19.

Donald C, Laddu A, Chandham P, Lim S, Cohen C, Amin M . Expression of progranulin and the epithelin/granulin precursor acrogranin correlates with neoplastic state in renal epithelium. Anticancer Res. 2002; 21(6A):3739-42. View

20.

Zhang X, Pan Z, Liu H, Yu J, Li G, Wang H . Effect of progranulin (PGRN) on the proliferation and senescence of cervical cancer cells. Genet Mol Res. 2015; 14(4):14331-8. DOI: 10.4238/2015.November.13.18. View