Molecular Signature of Prospero Homeobox 1 (PROX1) in Follicular Thyroid Carcinoma Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2019 May 8

PMID 31060342

Citations 8

Authors

Magdalena Rudzinska

Malgorzata Grzanka

Anna Stachurska

Michal Mikula

Katarzyna Paczkowska

Tomasz Stepien

Agnieszka Paziewska

Jerzy Ostrowski

Barbara Czarnocka

Affiliations

Soon will be listed here.

Abstract

The prospero homeobox 1 (PROX1) transcription factor is a product of one of the lymphangiogenesis master genes. It has also been suggested to play a role in carcinogenesis, although its precise role in tumour development and metastasis remains unclear. The aim of this study was to gain more knowledge on the PROX1 function in thyroid tumorigenesis. Follicular thyroid cancer-derived cells-CGTH-W-1-were transfected with PROX1-siRNA (small interfering RNA) and their proliferation, cell cycle, apoptosis and motility were then analysed. The transcriptional signature of depletion was determined using RNA-Sequencing (RNA-Seq) and the expression of relevant genes was further validated using reverse transcriptase quantitative PCR (RT-qPCR), Western blot and immunocytochemistry. PROX1 depletion resulted in a decreased cell motility, with both migratory and invasive potential being significantly reduced. The cell morphology was also affected, while the other studied cancer-related cell characteristics were not significantly altered. RNA-seq analysis revealed significant changes in the expression of transcripts encoding genes involved in both motility and cytoskeleton organization. Our transcriptional analysis of depleted follicular thyroid carcinoma cells followed by functional and phenotypical analyses provide, for the first time, evidence that PROX1 plays an important role in the metastasis of thyroid cancer cells by regulating genes involved in focal adhesion and cytoskeleton organization in tumour cells.

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References

Banerji S, Ni J, Wang S, Clasper S, Su J, Tammi R . LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. J Cell Biol. 1999; 144(4):789-801. PMC: 2132933. DOI: 10.1083/jcb.144.4.789. View

Soleiman A, Horvat R, Amann G, Kowalski H, Kerjaschki D . [Podoplanin--a specific marker for lymphatic endothelium expressed in angiosarcoma]. Verh Dtsch Ges Pathol. 2000; 83:270-5. View

Duncan M, Cui W, Oh D, Tomarev S . Prox1 is differentially localized during lens development. Mech Dev. 2002; 112(1-2):195-8. DOI: 10.1016/s0925-4773(01)00645-1. View

Lee H, Park D, Wang X, Scherer P, Schwartz P, Lisanti M . Src-induced phosphorylation of caveolin-2 on tyrosine 19. Phospho-caveolin-2 (Tyr(P)19) is localized near focal adhesions, remains associated with lipid rafts/caveolae, but no longer forms a high molecular mass hetero-oligomer with caveolin-1. J Biol Chem. 2002; 277(37):34556-67. DOI: 10.1074/jbc.M204367200. View

Burke Z, Oliver G . Prox1 is an early specific marker for the developing liver and pancreas in the mammalian foregut endoderm. Mech Dev. 2002; 118(1-2):147-55. DOI: 10.1016/s0925-4773(02)00240-x. View

Hong Y, Harvey N, Noh Y, Schacht V, Hirakawa S, Detmar M . Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate. Dev Dyn. 2002; 225(3):351-7. DOI: 10.1002/dvdy.10163. View

Nagai H, Li Y, Hatano S, Toshihito O, Yuge M, Ito E . Mutations and aberrant DNA methylation of the PROX1 gene in hematologic malignancies. Genes Chromosomes Cancer. 2003; 38(1):13-21. DOI: 10.1002/gcc.10248. View

Warren D, Zhang Q, Weissberg P, Shanahan C . Nesprins: intracellular scaffolds that maintain cell architecture and coordinate cell function?. Expert Rev Mol Med. 2005; 7(11):1-15. DOI: 10.1017/S1462399405009294. View

Tammela T, Petrova T, Alitalo K . Molecular lymphangiogenesis: new players. Trends Cell Biol. 2005; 15(8):434-41. DOI: 10.1016/j.tcb.2005.06.004. View

10.

Giordano T, Kuick R, Thomas D, Misek D, Vinco M, Sanders D . Molecular classification of papillary thyroid carcinoma: distinct BRAF, RAS, and RET/PTC mutation-specific gene expression profiles discovered by DNA microarray analysis. Oncogene. 2005; 24(44):6646-56. DOI: 10.1038/sj.onc.1208822. View

11.

Wang J, Kilic G, Aydin M, Burke Z, Oliver G, Sosa-Pineda B . Prox1 activity controls pancreas morphogenesis and participates in the production of "secondary transition" pancreatic endocrine cells. Dev Biol. 2005; 286(1):182-94. DOI: 10.1016/j.ydbio.2005.07.021. View

12.

Song K, Li T, Chiang J . A Prospero-related homeodomain protein is a novel co-regulator of hepatocyte nuclear factor 4alpha that regulates the cholesterol 7alpha-hydroxylase gene. J Biol Chem. 2006; 281(15):10081-8. PMC: 1785292. DOI: 10.1074/jbc.M513420200. View

13.

Giordano T, Au A, Kuick R, Thomas D, Rhodes D, Wilhelm Jr K . Delineation, functional validation, and bioinformatic evaluation of gene expression in thyroid follicular carcinomas with the PAX8-PPARG translocation. Clin Cancer Res. 2006; 12(7 Pt 1):1983-93. DOI: 10.1158/1078-0432.CCR-05-2039. View

14.

Shimoda M, Takahashi M, Yoshimoto T, Kono T, Ikai I, Kubo H . A homeobox protein, prox1, is involved in the differentiation, proliferation, and prognosis in hepatocellular carcinoma. Clin Cancer Res. 2006; 12(20 Pt 1):6005-11. DOI: 10.1158/1078-0432.CCR-06-0712. View

15.

Laerm A, Helmbold P, Goldberg M, Dammann R, Holzhausen H, Ballhausen W . Prospero-related homeobox 1 (PROX1) is frequently inactivated by genomic deletions and epigenetic silencing in carcinomas of the bilary system. J Hepatol. 2006; 46(1):89-97. DOI: 10.1016/j.jhep.2006.07.033. View

16.

Su J, Yen C, Chen P, Chuang S, Hong C, Kuo I . The role of the VEGF-C/VEGFR-3 axis in cancer progression. Br J Cancer. 2006; 96(4):541-5. PMC: 2360045. DOI: 10.1038/sj.bjc.6603487. View

17.

Versmold B, Felsberg J, Mikeska T, Ehrentraut D, Kohler J, Hampl J . Epigenetic silencing of the candidate tumor suppressor gene PROX1 in sporadic breast cancer. Int J Cancer. 2007; 121(3):547-54. DOI: 10.1002/ijc.22705. View

18.

Makinen T, Norrmen C, Petrova T . Molecular mechanisms of lymphatic vascular development. Cell Mol Life Sci. 2007; 64(15):1915-29. PMC: 11136057. DOI: 10.1007/s00018-007-7040-z. View

19.

Sundar S, Ganesan T . Role of lymphangiogenesis in cancer. J Clin Oncol. 2007; 25(27):4298-307. DOI: 10.1200/JCO.2006.07.1092. View

20.

Dudas J, Mansuroglu T, Moriconi F, Haller F, Wilting J, Lorf T . Altered regulation of Prox1-gene-expression in liver tumors. BMC Cancer. 2008; 8:92. PMC: 2359759. DOI: 10.1186/1471-2407-8-92. View