Copy number gains of the putative CRKL oncogene in laryngeal squamous cell carcinoma result in strong nuclear expression of the protein and influence cell proliferation and migration

被引:5
|
作者
Kostrzewska-Poczekaj, Magdalena [1 ]
Bednarek, Kinga [1 ]
Jarmuz-Szymczak, Malgorzata [1 ,2 ]
Bodnar, Magdalena [3 ,4 ]
Filas, Violeta [5 ,6 ]
Marszalek, Andrzej [5 ,6 ]
Bartochowska, Anna [4 ]
Grenman, Reidar [7 ,8 ]
Kiwerska, Katarzyna [1 ,9 ]
Szyfter, Krzysztof [1 ]
Giefing, Maciej [1 ]
机构
[1] Polish Acad Sci, Inst Human Genet, Poznan, Poland
[2] Poznan Univ Med Sci, Dept Hematol & Bone Marrow Transplantat, Poznan, Poland
[3] Nicolaus Copernicus Univ Torun, Coll Med Bydgoszcz, Dept Clin Pathomorphol, Bydgoszcz, Poland
[4] Univ Med Sci, Dept Otolaryngol & Laryngol Oncol, Poznan, Poland
[5] Poznan Univ Med Sci, Dept Oncol Pathol & Prophylaxis, Poznan, Poland
[6] Greater Poland Canc Ctr, Poznan, Poland
[7] Turku Univ, Cent Hosp, Dept Otorhinolaryngol Head & Neck Surg, Turku, Finland
[8] Turku Univ, Turku, Finland
[9] Greater Poland Canc Ctr, Dept Tumor Pathol, Poznan, Poland
关键词
GROWTH-FACTOR RECEPTOR; METASTATIC HEAD; OVEREXPRESSION; RECURRENT; AMPLIFICATION; CANCER;
D O I
10.1038/s41598-019-56870-5
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Laryngeal squamous cell carcinoma is a major medical problem worldwide. Although our understanding of genetic changes and their consequences in laryngeal cancer has opened new therapeutic pathways over the years, the diagnostic as well as treatment options still need to be improved. In our previous study, we identified CRKL (22q11) as a novel putative oncogene overexpressed and amplified in a subset of LSCC tumors and cell lines. Here we analyze to what extent CRKL DNA copy number gains correlate with the higher expression of CRKL protein by performing IHC staining of the respective protein in LSCC cell lines (n = 3) and primary tumors (n = 40). Moreover, the importance of CRKL gene in regard to proliferation and motility of LSCC cells was analyzed with the application of RNA interference (siRNA). Beside the physiological cytoplasmic expression, the analysis of LSCC tumor samples revealed also nuclear expression of CRKL protein in 10/40 (25%) cases, of which three (7.5%), presented moderate or strong nuclear expression. Similarly, we observed a shift towards aberrantly strong nuclear abundance of the CRKL protein in LSCC cell lines with gene copy number amplifications. Moreover, siRNA mediated silencing of CRKL gene in the cell lines showing its overexpression, significantly reduced proliferation (p < 0.01) as well as cell migration (p < 0.05) rates. Altogether, these results show that the aberrantly strong nuclear localization of CRKL is a seldom but recurrent phenomenon in LSCC resulting from the increased DNA copy number and overexpression of the gene. Moreover, functional analyses suggest that proliferation and migration of the tumor cells depend on CRKL expression.
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页数:9
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