Dysregulated AKT signaling reprograms osteosarcoma to drive selective reliance on EP300

Inhibition of PI3K or AKT Differently Regulates Mesodermal Differentiation in P19CL6 Cells

Simple Summary Inhibition of the PI3K pathway promotes mesodermal differentiation, whereas inhibition of the AKT pathway does the opposite. Mechanistic studies demonstrate that inhibition of the PI3K pathway activates the Wnt/β-catenin signaling pathway. Inhibition of the PI3K pathway can promote the expression of gene...

RSPO1–LGR4 axis drives cervical cancer progression via activation of the EGFR/Src/ERK/AKT signaling pathway

Highlights • RSPO1 is upregulated in cervical cancer.• RSPO1 promotes proliferation, migration, invasion, and tumorigenesis in vitro/vivo.• RSPO1 activates EGFR/Src/ERK/AKT axis via LGR4 in cervical cancer.• RSPO1-LGR4 stabilizes EGFR by blocking c-Cbl-mediated ubiquitination/degradation.

Matrine Suppresses Osteosarcoma Lung Metastasis by Targeting the PI3K/AKT Signaling Pathway to Induce Mitochondrial Dysfunction

Simple Summary Osteosarcoma survival drops to ~20% after lung metastasis, highlighting the need for new therapies. This study shows that matrine, a natural compound from Sophora flavescens, suppresses osteosarcoma growth and lung metastasis in vitro and in vivo by directly inhibiting PI3K/AKT signaling, thereby inducin...

A genetically regulated SKAP2 switch modulates human T lymphocyte adhesion and migration

Spinella et al. linked a Crohn’s disease risk allele regulating SKAP2 expression to T lymphocyte function. SKAP2 enhances cell adhesion while suppressing migration. Sustained TCR signaling triggers its proteolytic cleavage to enable migration. Overall, genetic alteration of SKAP2 levels drives T cell dysfunction and pr...

Intrinsic resistance to KRAS inhibition: Interfering with interferon.

In this issue of Cancer Cell, Zhang et al. perform multi-omics profiling on a large collection of patient-derived pancreatic ductal adenocarcinoma organoids to elucidate the mechanisms underlying intrinsic resistance to KRAS inhibition. This work identifies suppression of innate immune signaling through sustained MYC a...

NPM1 drives cancer cell migration and invasion by amplifying EGFR gene expression and its downstream signaling