Down-regulation of the Tumor Suppressor CYLD Enhances the Transformed Phenotype of Human Breast Cancer Cells.
BACKGROUND/AIM
The cylindromatosis tumor suppressor (CYLD) has been implicated in the inhibition of human breast cancer development by virtue of the poor prognosis of patients with down-regulated CYLD expression. In order to investigate the mechanism of breast cancer suppression by CYLD, in the present study, cellular and molecular aspects of CYLD-dependent phenotypic regulation of different types of human breast cancer cell lines were analyzed.


MATERIALS AND METHODS
CYLD expression was down-regulated by RNA interference in human breast cancer cell lines. Parental and CYLD-deficient cell lines were evaluated for their viability, migratory capacity, anchorage-independent growth and chemoresistance. Wild-type and mutated forms of CYLD were also evaluated for their ability to suppress the clonogenic potential of breast cancer cells.


RESULTS
CYLD down-regulation enhanced the survival and migratory properties of basal and luminal breast cancer cell lines. In addition, down-regulation of CYLD expression enhanced the ability of human breast cancer cells to grow in an anchorage-independent manner and could be associated with resistance to chemotherapeutic drugs. The growth-suppressive properties of CYLD on breast cancer cell lines were dependent on its de-ubiquitinating activity and its amino terminal cytoskeleton-interacting region.


CONCLUSION
Our results establish a broad range of tumor-suppressive properties that are conferred by CYLD in basal and luminal human breast cancer cells and support the significance of targeted de-ubiquitination by CYLD in breast cancer cell growth suppression.
['Orfanidou|Timoklia|T|', 'Xanthopoulos|Konstantinos|K|', 'Dafou|Dimitra|D|', 'Pseftogas|Athanasios|A|', 'Hadweh|Paul|P|', 'Psyllaki|Claire|C|', 'Hatzivassiliou|Eudoxia|E|', 'Mosialos|George|G|']
D001943:Breast Neoplasms D002460:Cell Line D045744:Cell Line, Tumor D002465:Cell Movement D002470:Cell Survival D003599:Cytoskeleton D000074749:Deubiquitinating Enzyme CYLD D015536:Down-Regulation D019008:Drug Resistance, Neoplasm D005260:Female D016147:Genes, Tumor Suppressor D057809:HEK293 Cells D006801:Humans D061986:MCF-7 Cells D034622:RNA Interference D025521:Tumor Suppressor Proteins D054875:Ubiquitination
tumor suppressor CYLD transformation breast cancer signal transduction