The expression and oncogenic effects of the embryonic stem cell marker SALL4 in ALK-positive anaplastic large cell lymphoma
| Autor: | Jianchang Yang, Pascal Gélébart, David Sharon, Xiaoxia Ye, Todd P. W. McMullen, Raymond Lai, Fang Wu, Yupo Ma, Samar A. Hegazy, Peng Wang, Jingdong Zhang, Mary M. Hitt |
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| Rok vydání: | 2012 |
| Předmět: |
STAT3 Transcription Factor
Apoptosis Biology SALL4 hemic and lymphatic diseases Cell Line Tumor medicine Anaplastic lymphoma kinase Humans Lymphocytes RNA Small Interfering Anaplastic large-cell lymphoma Cell Proliferation Cell growth Large cell Cell Biology Cell Cycle Checkpoints Protein-Tyrosine Kinases medicine.disease Embryonic stem cell eye diseases Gene Expression Regulation Neoplastic Cell culture Caspases Gene Knockdown Techniques Cancer research Lymphoma Large-Cell Anaplastic RNA Interference Apoptosis Regulatory Proteins Adult stem cell Transcription Factors |
| Zdroj: | Cellular signalling. 24(10) |
| ISSN: | 1873-3913 |
| Popis: | SALL4 is one of the master transcriptional factors that are crucial in maintaining the pluripotency of embryonic stem cells (ESCs). While the expression of SALL4 is normally restricted to ESCs and somatic stem cells, we found that it is aberrantly expressed in ALK-positive anaplastic large cell lymphoma (ALK+ ALCL), a type of lymphoid malignancy carrying a mature T-cell immunophenotype. shRNA knockdown of SALL4 in ALK+ ALCL cell lines resulted in apoptosis and cell-cycle arrest, and significantly decreased colony formation on soft agar. These changes correlated with the downregulation of several anti-apoptotic proteins and facilitators of cell-cycle progression. Based on the differential response to a SALL4 reporter construct, we were able to separate two distinct cell subsets in Karpas 299 (an ALK+ ALCL cell line), namely SALL4(high) and SALL4(low). Importantly, the biological effects induced by SALL4 knock-down in Karpas 299 were restricted to the purified SALL4(high) cells, and this finding further supports the concept that SALL4 is biologically important in ALK+ ALCL. Lastly, the expression of SALL4 was not dependent on the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK)/STAT3 signaling axis, the key oncogenic driver in ALK+ ALCL. To conclude, for the first time, our study has revealed the oncogenic contributions of an ESC protein in the pathogenesis of ALK+ ALCL. |
| Databáze: | OpenAIRE |
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