A mix of S and [Delta]S variants of STAT3 enable survival of activated B-cell-like diffuse large B-cell lymphoma cells in culture

• Published in: Oncogenesis (New York, NY) Vol. 5; p. e184
• Main Authors: Zheng, M, Turton, K B, Zhu, F, Li, Y, Grindle, K M, Annis, D S, Lu, L, Drennan, A C, Tweardy, D J, Bharadwaj, U, Mosher, D F, Rui, L
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group 01.01.2016
• Subjects: Cellular biology; Lymphomas
• ISSN: 2157-9024
• DOI: 10.1038/oncsis.2015.44

Activated B-cell-like diffuse large B-cell lymphoma (ABC DLBCL) is characterized by increased expression and activator of signal transducer and activator of transcription 3 (STAT3). ABC DLBCL cells require STAT3 for growth in culture. In ABC DLBCL cells, eosinophils and perhaps all cells, four variant STAT3 mRNAs (S, S, S and S) are present as a result of two alternative splicing events, one that results in the inclusion of a 55-residue C-terminal transactivation domain () or a truncated C-terminal domain with 7 unique residues () and a second that includes (S) or excludes (S) the codon for Ser-701 in the linker between the SH2 and C-terminal domains. A substantial literature indicates that both and variants are required for optimal STAT3 function, but nothing is known about functions of S variants. We used a knockdown/re-expression strategy to explore whether survival of ABC DLBCL cells requires that the four variants be in an appropriate ratio. No single variant rescued survival as well as STAT3S-C, S with activating mutations (A661C and N663C) in the SH2 domain. Better rescue was achieved when all four variants were re-expressed or S and S or S and S were re-expressed in pairs. Rescue correlated with expression of STAT3-sensitive genes NFKBIA and NFKBIZ. We consider a variety of explanations why a mix of S and S variants of STAT3 should enable survival of ABC DLBCL cells.