Abstract
Abstract Inappropriate expression and function of cytokine and chemokine receptors by both hematopoietic and non-hematopoietic cell populations have been linked to human disease. One example of this is the expression of lymphocytic genes by metastatic cancers, termed lymphocyte mimicry. Specifically, the aberrant expression of chemokine receptors by cancer cells allows for inappropriate responses to immune signals, migration, and increased ability to survive in circulation. The mechanisms that regulate lymphocyte mimicry are currently incompletely understood. Our laboratory recently identified a novel transcriptional complex composed of the Ikaros Zinc Finger transcription factor Aiolos and STAT3 that regulates gene expression in CD4+ T cells, including that of chemokine receptors. Interestingly, Aiolos and STAT3 have been independently implicated in multiple cancers, including metastatic breast cancer. We hypothesized that Aiolos and STAT3 may cooperate to induce chemokine receptor expression in metastatic breast cancer cells. Our study observed increased Aiolos expression and STAT3 activation in metastatic breast cancer cells as compared to non-tumorgenic and non-metastatic controls. This correlated with increased expression of the chemokine receptor CXCR4, which has been previously linked to metastatic cancer. Importantly, shRNA knockdown of Aiolos in metastatic cells resulted in decreased expression of CXCR4. Collectively, these data support a role for Aiolos, possibly in collaboration with STAT3, in the induction of a metastatic gene signature in human breast cancer.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.