Resolving the role of podoplanin in the motility of papillary thyroid carcinoma-derived cells using RNA sequencing.

Autor:	Mielecki D; Centre of Postgraduate Medical Education, Department of Cell Biology and Immunology, Marymoncka 99/103, 01-813 Warsaw, Poland., Gajda E; Centre of Postgraduate Medical Education, Department of Cell Biology and Immunology, Marymoncka 99/103, 01-813 Warsaw, Poland., Sikorska J; Centre of Postgraduate Medical Education, Department of Cell Biology and Immunology, Marymoncka 99/103, 01-813 Warsaw, Poland., Betkowska A; Centre of Postgraduate Medical Education, Department of Cell Biology and Immunology, Marymoncka 99/103, 01-813 Warsaw, Poland., Rozwadowski M; Centre of Postgraduate Medical Education, Department of Cell Biology and Immunology, Marymoncka 99/103, 01-813 Warsaw, Poland., Gawel AM; Medical University of Warsaw, Histology and Embryology Students Science Association at the Department for Histology and Embryology, Chalubinskiego 5, 02-004 Warsaw, Poland., Kulecka M; Centre of Postgraduate Medical Education, Department of Gastroenterology, Hepatology and Clinical Oncology, Marymoncka 99/103, 01-813 Warsaw, Poland., Zeber-Lubecka N; Centre of Postgraduate Medical Education, Department of Gastroenterology, Hepatology and Clinical Oncology, Marymoncka 99/103, 01-813 Warsaw, Poland., Godlewska M; Centre of Postgraduate Medical Education, Department of Cell Biology and Immunology, Marymoncka 99/103, 01-813 Warsaw, Poland., Gawel D; Centre of Postgraduate Medical Education, Department of Cell Biology and Immunology, Marymoncka 99/103, 01-813 Warsaw, Poland.
Jazyk:	angličtina
Zdroj:	Computational and structural biotechnology journal [Comput Struct Biotechnol J] 2023 Jul 26; Vol. 21, pp. 3810-3826. Date of Electronic Publication: 2023 Jul 26 (Print Publication: 2023).
DOI:	10.1016/j.csbj.2023.07.035
Abstrakt:	The intracellular level of podoplanin (PDPN), a transmembrane protein of still unclear function, is frequently altered in metastatic tumors. High expression of PDPN is frequently observed in papillary thyroid cancer (PTC) specimens. Similarly, PTC-derived cell lines (BCPAP and TPC1, harboring the BRAF V600E mutation and RET /PTC1 fusion, respectively), also present enhanced PDPN yield. We previously reported that depletion of PDPN impairs migration of TPC1 cells, but augments metastasis of BCPAP cells. Interestingly, this phenomenon stays in contrast to the migratory pattern observed for wild-type cells, where TPC1 exhibited higher motility than BCPAP cells. Here, we aimed to elucidate the potential role of PDPN in regulation of molecular mechanisms leading to the diverse metastatic features of the studied PTC-derived cells. We consider that this phenomenon may be caused by alternative regulation of signaling pathways due to the presence of the mutated  BRAF  allele or RET /PTC1 fusion. The high-throughput RNA sequencing (RNA-seq) technique was used to uncover the genes and signaling pathways affected in wild-type and PDPN -depleted TPC1 and BCPAP cells. We found that changes in the expression of various factors of signaling pathways, like RHOA and RAC1 GTPases and their regulators, are linked with both high PDPN levels and presence of the BRAF V600E mutation. We imply that the suppressed motility of wild-type BCPAP cells results from overactivation of RHOA through natively high PDPN expression. This process is accompanied by inhibition of the PI3K kinase and consequently RAC1, due to overactivation of RAS-mediated signaling and the PTEN regulator. (© 2023 The Authors.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu