| 2008 |
In PTEN-deficient cancer cells, PIK3CB (p110β) but not PIK3CA (p110α) is required to sustain PI3K pathway activation and cell growth; this essential function requires the lipid kinase activity of p110β, established by shRNA-mediated selective knockdown and kinase-dead rescue in cell-based and in vivo xenograft models. |
Inducible shRNA knockdown (lentiviral), cell growth assays, in vivo xenograft models, kinase-dead mutant rescue |
Proceedings of the National Academy of Sciences of the United States of America |
High |
18755892
|
| 2016 |
A PIK3CB D1067Y activating mutation confers resistance to pan-PI3K inhibition by elevating PIP3 levels at the cell membrane, promoting AKT and PDK1 membrane localization/activation; this mutant behaves as an oncogene and transforms normal cells, and resistance can be overcome by downstream AKT or mTORC1/2 inhibitors. |
Stable expression of mutant PIK3CB variants, PIP3 membrane imaging, AKT/PDK1 localization assays, cell transformation assays, pharmacological rescue with AKT/mTORC1/2 inhibitors |
Cancer research |
High |
26759240
|
| 2017 |
The PIK3CB catalytic domain mutant p110βE1051K (first identified in castrate-resistant prostate cancer) is a gain-of-function oncogenic mutation that drives PI3K signaling, tumorigenic cell growth, and migration; tumor cells expressing this mutant are sensitive to p110β-selective inhibition. |
Expression of mutant PIK3CB in cells, PI3K signaling assays, cell growth and migration assays, p110β-selective inhibitor treatment |
Signal transduction and targeted therapy |
Medium |
29279775
|
| 2021 |
PIK3CB (p110β) wild-type overexpression transforms MCF-10A epithelial cells through a signaling loop requiring direct binding to RAC1; p110β-induced transformation involves RAC1 hyperactivation, lamellipodia formation, and a partial EMT (E-cadherin maintained, delamination occurs), distinct from the PIK3CA H1047R-induced phenotype; a Rac1-binding mutant of p110β abolished transformation. |
MCF-10A overexpression model, Rac1-binding mutant of p110β (loss-of-function mutagenesis), morphological and migration assays, immunofluorescence for lamellipodia/filopodia, RAC1 activation assay, PI3K-AKT signaling assays |
Journal of cell science |
High |
33526718
|
| 2020 |
m6A methylation of PIK3CB mRNA by the METTL3/METTL14/WTAP writer complex is read by YTHDF2, suppressing PIK3CB mRNA and protein expression; a missense variant rs142933486 in PIK3CB reduces this m6A modification, elevating PIK3CB expression and activating AKT signaling to promote PTEN-deficient PDAC progression. |
m6A methylation assays, METTL3/METTL14/WTAP and YTHDF2 functional studies, in vitro and in vivo PDAC models, PIK3CB-selective inhibitor KIN-193 treatment |
Gut |
Medium |
32312789
|
| 2007 |
A C/T variant (rs361072) in the PIK3CB promoter creates a GATA-binding site; the C allele drives increased PIK3CB transcription as shown by GATA-binding assays and reporter transfection, and is associated with reduced insulin resistance (lower HOMA-IR) in obese children, identifying PIK3CB as a cis-acting eQTL for insulin sensitivity. |
GATA-binding assays, promoter-reporter transfection in cell lines, lymphocyte expression quantification, population genetic association (HOMA-IR measurement) |
Diabetes |
Medium |
17977952
|
| 2017 |
In a rat subarachnoid hemorrhage model, ErbB4 activation increases YAP expression, which in turn elevates PIK3CB levels; YAP knockdown reduces PIK3CB expression and abolishes the anti-apoptotic effect of ErbB4 activation, placing PIK3CB downstream of ErbB4/YAP in a neuroprotective signaling pathway. |
ErbB4 siRNA, YAP siRNA, ErbB4 activator (Nrg1β1), immunofluorescence, neurological scoring, rat SAH model |
Experimental neurology |
Low |
28756200
|
| 2024 |
PDCD4 binds to the IRES element in the 5' UTR of PIK3CB mRNA (confirmed by RNA pull-down and dual luciferase reporter assay), inhibiting PIK3CB translation; PDCD4 knockdown reduces apoptosis in multiple myeloma cells, which is rescued by PIK3CB inhibitors, indicating PDCD4 suppresses PIK3CB protein production to promote apoptosis. |
RNA-binding protein immunoprecipitation sequencing, dual luciferase IRES reporter assay, RNA pull-down assay, PDCD4 knockdown/overexpression, in vitro and in vivo apoptosis assays |
FASEB journal |
Medium |
39190024
|
| 2024 |
SP1 transcription factor binds the -771 to -605 region of the PIK3CB promoter (confirmed by ChIP and dual-luciferase assay), activating PIK3CB transcription and driving AKT activation to promote gastric cancer cell proliferation and migration. |
Chromatin immunoprecipitation (ChIP), dual-luciferase promoter reporter assay, PIK3CB knockdown/overexpression, SP1 knockdown, AKT phosphorylation assays, PIK3CB inhibitor TGX-221 |
Journal of Cancer |
Medium |
38356702
|
| 2021 |
PIK3CB depletion inhibits invasion specifically by suppressing cell adhesion to collagen I in pancreatic cancer cells, and significantly reduces metastatic potential in vivo in nude mice. |
PIK3CB knockdown, collagen I adhesion assays, invasion assays, in vivo metastasis model (nude mice), bioinformatic pathway analysis |
Journal of advanced research |
Medium |
34603784
|
| 2021 |
LukS-PV induces apoptosis in AML cells by downregulating the histone methyltransferase SET8 and its product H4K20me1; ChIP-seq identified PIK3CB as a downstream transcriptional target of the SET8/H4K20me1 mark, placing PIK3CB in a SET8→H4K20me1→PIK3CB→AKT→FOXO1 apoptosis signaling axis. |
ChIP-seq, SET8 knockdown, H4K20me1 ChIP-PCR, LukS-PV treatment, AKT/FOXO1 signaling assays, apoptosis assays |
Frontiers in oncology |
Medium |
34745943
|
| 2024 |
PTK7 physically interacts with PIK3CB (confirmed by Co-IP), and USP8-mediated deubiquitination of PTK7 stabilizes PTK7 protein, which in turn positively regulates PIK3CB expression to activate the PI3K/AKT pathway and promote NSCLC malignant progression. |
Co-immunoprecipitation (Co-IP), PTK7/USP8 knockdown, PIK3CB overexpression rescue, western blot (PI3K/AKT), in vivo xenograft |
Thoracic cancer |
Low |
39552193
|
| 2025 |
hnRNPL forms phase-separated condensates at the PIK3CB promoter to activate PIK3CB transcription; this drives glycolysis and ovarian cancer progression. A non-coding RNA transcribed from the PIK3CB promoter itself interacts with hnRNPL and promotes hnRNPL condensation, creating a positive feedback loop. |
ChIP, phase separation assays, hnRNPL knockdown/overexpression, PIK3CB promoter reporter, RNA–protein interaction assays, glycolysis measurement, cell-derived xenograft and patient-derived organoid models |
Nature communications |
Medium |
40413189
|
| 2018 |
PIK3CB (p110β) is the dominant PI3K isoform controlling PI3K signaling in GBM cells; blocking p110β with shRNA or isoform-selective inhibitors deactivates PI3K signaling and suppresses GBM cell viability, growth, and xenograft tumor growth, whereas inhibition of other PI3K isoforms had no effect. |
shRNA knockdown, isoform-selective inhibitors, MTS/trypan blue viability assays, caspase activity assay, mouse xenograft models, immunoblotting |
Neuro-oncology |
Medium |
29016844
|
| 2010 |
In PTEN-deficient glioblastoma cells, PIK3CB knockdown (but not PIK3CA knockdown) reduces pAKT levels, inhibits proliferation, arrests cell cycle at G0/G1, and promotes caspase-dependent apoptosis; combined PTEN restoration and PIK3CB knockdown shows strong synergy in vitro and completely suppresses xenograft tumor growth. |
siRNA knockdown of PIK3CB vs. PIK3CA, PTEN restoration, AKT phosphorylation western blot, cell cycle analysis, apoptosis assay, nude mouse xenograft |
Journal of neuro-oncology |
Medium |
21188471
|