Transforming acidic coiled-coil 3 and Aurora-A interact in human thyrocytes and their expression is deregulated in thyroid cancer tissues.
Aurora-A kinase has recently been shown to be deregulated in thyroid cancer cells and tissues. Among the Aurora-A substrates identified, transforming acidic coiled-coil (TACC3), a member of the TACC family, plays an important role in cell cycle progression and alterations of its expression occur in different cancer tissues. In this study, we demonstrated the expression of the TACC3 gene in normal human thyroid cells (HTU5), and its modulation at both mRNA and protein levels during cell cycle. Its expression was found, with respect to HTU5 cells, unchanged in cells derived from a benign thyroid follicular tumor (HTU42), and significantly reduced in cell lines derived from follicular (FTC-133), papillary (B-CPAP), and anaplastic thyroid carcinomas (CAL-62 and 8305C). Moreover, in 16 differentiated thyroid cancer tissues, TACC3 mRNA levels were found, with respect to normal matched tissues, reduced by twofold in 56% of cases and increased by twofold in 44% of cases. In the same tissues, a correlation between the expression of the TACC3 and Aurora-A mRNAs was observed. TACC3 and Aurora-A interact in vivo in thyroid cells and both proteins localized onto the mitotic structure of thyroid cells. Finally, TACC3 localization on spindle microtubule was no more observed following the inhibition of Aurora kinase activity by VX-680. We propose that Aurora-A and TACC3 interaction is important to control the mitotic spindle organization required for proper chromosome segregation.
Ulisse
Salvatore
S
Department of Experimental Medicine, University of Rome La Sapienza, Rome, Italy.
Baldini
Enke
E
Toller
Matteo
M
Delcros
Jean-Guy
JG
Guého
Aurélie
A
Curcio
Francesco
F
De Antoni
Enrico
E
Giacomelli
Laura
L
Ambesi-Impiombato
Francesco S
FS
Bocchini
Sarah
S
D'Armiento
Massimino
M
Arlot-Bonnemains
Yannick
Y
D000328:Adult; D000368:Aged; D064127:Aurora Kinases; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics; D002478:Cells, Cultured; D018385:Centrosome / Q000187:drug effects / Q000378:metabolism; D020090:Chromosome Segregation / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology; D011003:Ploidies; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D003521:Cyclopropanes; D011720:Pyrazoles; D011743:Pyrimidines
D064127:Aurora Kinases; D008869:Microtubule-Associated Proteins; D010879:Piperazines; D017346:Protein Serine-Threonine Kinases; C120551:TACC3 protein, human; C484810:tozasertib; D003521:Cyclopropanes; D011720:Pyrazoles; D011743:Pyrimidines