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Co-targeting of ACK1 and KIT triggers additive anti-proliferative and -migration effects in imatinib-resistant gastrointestinal stromal tumors
Biochim Biophys Acta Mol Basis Dis. 2023 Mar 13:166690. doi: 10.1016/j.bbadis.2023.166690. Online ahead of print.ABSTRACTMost gastrointestinal stromal tumors (GIST) harbor mutated receptor tyrosine kinase (RTK) KIT/PDGFRA, which provides an attractive therapeutic target. However, a majority of GISTs ultimately develop resistance to KIT/PDGFRA inhibitor imatinib, multiple therapeutic targets will be identified as a reasonable strategy in imatinib-resistant GISTs. Biological mechanisms of non-RTK activated CDC42 associated kinase 1 (ACK1) are still unclear, which has been found to be activated in GISTs. In the current report...
Source: Biochimica et Biophysica Acta - March 15, 2023 Category: Biochemistry Authors: Wangzhen He Liangliang Xu Jiongyan Ding Li Song Weili Yang Isabella Klooster Daniel F Pilco-Janeta C ésar Serrano Hongming Fang Guojun Jiang Xiaoyan Wang Jiren Yu Wen-Bin Ou Source Type: research

Hypoxia inducible factor 1 α inhibitor induces cell death via suppression of BCR-ABL1 and Met expression in BCR-ABL1 tyrosine kinase inhibitor sensitive and resistant chronic myeloid leukemia cells
In this study, we examined whether HIF-1α inhibitors induce cell death in CML cells and BCR-ABL1 TKI-resistant CML cells. We found that echinomycin and PX-478 induced cell death in BCR-ABL1 TKIs sensitive and resistant CML cells at similar concentrations while the cell sensitivity was not affected with imatinib or dasatinib in BCR-ABL1 TKIs resistant CML cells. In addition, echinomycin and PX-478 inhibited the c-Jun N-terminal kinase (JNK), Akt, and extracellular-regulated protein kinase 1/2 (ERK1/2) activation via suppression of BCR-ABL1 and Met expression in BCR-ABL1 sensitive and resistant CML cells. Moreover, treatmen...
Source: BMB Reports - October 4, 2022 Category: Biochemistry Authors: Masanobu Tsubaki Tomoya Takeda Takuya Matsuda Akihiro Kimura Remi Tanaka Sakiko Nagayoshi Tadafumi Hoshida Kazufumi Tanabe Shozo Nishida Source Type: research

c-Abl phosphorylation of Yin Yang 1's conserved tyrosine 254 in the spacer region modulates its transcriptional activity.
In conclusion, we demonstrate the novel role of c-Abl kinase in regulation of YY1's transcriptional activity, linking YY1 regulation with c-Abl tyrosine kinase signaling pathways. PMID: 29807053 [PubMed - as supplied by publisher]
Source: Biochimica et Biophysica Acta - May 25, 2018 Category: Biochemistry Authors: Daraiseh SI, Kassardjian A, Alexander KE, Rizkallah R, Hurt MM Tags: Biochim Biophys Acta Source Type: research