SALL4B, not targeted by IMiD, is important for SALL4-mediated tumorigenesis
Vu, K. A. L.; Kumari, K.; Liu, B. H.; Gao, C.; Li, F.; Tang, J.; Maddalo, D.; Auld, D.; Casalena, D.; Tian, X.; Liu, M.; Bassal, M. A.; Moein, S.; Iakovleva, V.; Tan, J.; stein, a.; Zhou, Q.; Fischer, P.; Sigua, L.; Qi, J.; Arthanari, H.; Tenen, D.; Chai, L.
Show abstract
Oncofetal transcription factor SALL4 is essential for cancer cell survival.1-5 Recently, several groups reported that immunomodulatory imide drugs (IMiDs) could degrade SALL4 in a proteasome-dependent manner.6,7 Intriguingly, we observed that IMiDs had no effect on SALL4-positive cancer cells. Further studies demonstrated that IMiDs could only degrade SALL4A, one of the SALL4 isoforms. This finding raises the possibility that SALL4B, the isoform not affected by IMiDs, may be essential for SALL4-mediated cancer cell survival. SALL4B knockdown led to an increase in apoptosis and inhibition of cancer cell growth. SALL4B gain-of-function alone led to liver tumor formation in mice. Our observation that protein degraders can possess isoform-specific effects exemplifies the importance of delineating drug action and oncogenesis at the isoform level to develop more effective cancer therapeutics.
Matching journals
The top 12 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Small molecule mediated stabilization of PP2A modulates the Homologous Recombination pathway and potentiates DNA damage-induced cell death 95%
- Targeting aggressive B-cell lymphomas through pharmacological activation of the mitochondrial protease OMA1 95%
- Clinical positioning of the IAP antagonist tolinapant (ASTX660) in colorectal cancer 94%
Similar papers in this journal
- Histone deacetylase inhibitor induces acetyl-CoA depletion leading to lethal metabolic stress in RAS-pathway activated cells 94%
- The MEK1/2 pathway as a therapeutic target in high-grade serous ovarian carcinoma 94%
- Synthetic lethality screening identifies FDA-approved drugs that overcome ATP7B-mediated tolerance of tumor cells to cisplatin 94%
Similar papers in this journal
- Inhibiting BCKDK in triple-negative breast cancer suppress protein translation, impair mitochondrial function, and potentiate doxorubicin cytotoxicity 95%
- The CDK12 inhibitor SR-4835 functions as a molecular glue that promotes cyclin K degradation in melanoma 95%
- CDK8/19 Inhibition Attenuates G1 Arrest Induced by BCR-ABL Antagonists and Accelerates Death of Chronic Myelogenous Leukemia Cells 93%
Similar papers in this journal
- Evaluation of KRASG12C Inhibitor Responses in Novel Murine KRASG12C Lung Cancer Cell Line Models 94%
- Increased efficacy of histone methyltransferase G9a inhibitors against MYCN-amplified Neuroblastoma 93%
- Novel kinome profiling technology reveals drug treatment is patient and 2D/3D model dependent in GBM 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.