Targeted PI3K/AKT-Hyperactivation Induces Cell Death in Chronic Lymphocytic Leukemia

Scientists hypothesized that targeted hyperactivation of the phosphatidylinositol-3-phosphate/AKT (PI3K/AKT)-signaling pathway may have been leveraged to trigger chronic lymphocytic leukemia cell death.
[Nature Communications]
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Cabozantinib Promotes Erythroid Differentiation in K562 Erythroleukemia Cells through Global Changes in Gene Expression and JNK Activation

The authors reported that cabozantinib could promote differentiation in erythroid leukemia cells and found that K562 erythroid leukemia cells treated with 1 μM cabozantinib for 72 hours underwent erythroid lineage differentiation.
[Cancer Gene Therapy]
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Depalmitoylation Rewires FLT3-ITD Signaling and Exacerbates Leukemia Progression

Investigators discovered that FLT3-ITD, one of the most frequent mutations in acute myeloid leukemia, was S-palmitoylated by the ZDHHC6 palmitoyl acyltransferase. Disruption of palmitoylation redirected FLT3-ITD to the plasma membrane and rewired its downstream signaling by activating AKT and ERK pathways in addition to STAT5.
[Blood]
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Novel Induction of CD40 Expression by Tumor Cells with RAS/RAF/PI3K Pathway Inhibition Augments Response to Checkpoint Blockade

Rigosertib monotherapy or in combination therapy with immune checkpoint blockade were investigated using immunocompetent mouse models of BRAFwt and BRAFmut melanoma and analyzed in reference to patient data.
[Molecular Cancer]
Yan, C., Saleh, N., Yang, J., Nebhan, C. A., Vilgelm, A. E., Reddy, E. P., Roland, J. T., Johnson, D. B., Chen, S.-C., Shattuck-Brandt, R. L., Ayers, G. D., & Richmond, A. (2021). Novel induction of CD40 expression by tumor cells with RAS/RAF/PI3K pathway inhibition augments response to checkpoint blockade. Molecular Cancer, 20(1), 85. https://doi.org/10.1186/s12943-021-01366-y Cite
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D-Dopachrome Tautomerase Contributes to Lung Epithelial Repair via Atypical Chemokine Receptor 3-Dependent Akt Signaling

Investigators studied effects of recombinant D-dopachrome tautomerase (DDT) on cell proliferation and survival by clonogenic assay and annexin V-PI staining respectively. DDT-induced signaling was investigated by Western blot.
[Ebiomedicine]
Song, S., Liu, B., Habibie, H., Bor, J. van den, Smit, M. J., Gosens, R., Wu, X., Brandsma, C.-A., Cool, R. H., Haisma, H. J., Poelarends, G. J., & Melgert, B. N. (2021). D-dopachrome tautomerase contributes to lung epithelial repair via atypical chemokine receptor 3-dependent Akt signaling. EBioMedicine, 68. https://doi.org/10.1016/j.ebiom.2021.103412 Cite
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LncRNA Bmp1 Promotes the Healing of Intestinal Mucosal Lesions via the miR-128-3p/PHF6/PI3K/AKT Pathway

The authors investigated the mechanisms of action of long non-coding RNA Bmp1 on damaged intestinal mucosa. They found that Bmp1 was increased in damaged intestinal mucosal tissue and Bmp1 overexpression was able to alleviate intestinal mucosal injury.
[Cell Death & Disease]
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Combined Inhibition of DDR1 and CDK4/6 Induces Synergistic Effects in ER-Positive, HER2-Negative Breast Cancer with PIK3CA/AKT1 Mutations

DDR1 knockdown and DDR1 pharmacological inhibitor decreased cell growth and inhibited cell cycle progression in breast cancer cell lines, while enhanced the sensitivity of PIK3CA/AKT1 mutant cells to palbociclib.
[Oncogene]
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The Combination of Cudc-907 and Gilteritinib Shows Promising In Vitro and In Vivo Antileukemic Activity against FLT3-Itd AML

Investigators showed that gilteritinib and CUDC-907, a dual inhibitor of PI3K and histone deacetylases, synergistically induced apoptosis in FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) acute myeloid leukemia (AML) cell lines and primary patient samples and had striking in vivo efficacy.
[Blood Cancer Journal]
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The N6-Methyladenosine Demethylase ALKBH5 Negatively Regulates the Osteogenic Differentiation of Mesenchymal Stem Cells through PRMT6

Researchers showed that conditional knockout of the demethylase Alkbh5 in bone marrow MSCs strengthened bone mass in mice.
[Cell Death & Disease]
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Tracing Oncogene-Driven Remodelling of the Intestinal Stem Cell Niche

Scientists applied an oncogene-associated, multicolor reporter mouse model to the small intestine to show that oncogene-expressing mutant crypts altered the cellular organization of neighbouring wild-type crypts, thereby driving accelerated clonal drift.
[Nature]
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The PI3K/mTOR Inhibitor Gedatolisib Eliminates Dormant Breast Cancer Cells in Organotypic Culture, but Fails to Prevent Metastasis in Preclinical Settings

By probing a number of kinases downstream of integrin-β1, scientists determined that PI3K inhibition with either a tool compounds or a compound in clinical trials robustly sensitizes quiescent breast tumor cells seeded in organotypic bone marrow cultures to chemotherapy.
[Molecular Oncology]
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