| Expression pattern: |
UP |
| Associated gene: |
GRB7, FAK, Pin1, HER2, AKT, ERK1/2 |
| Associated microRNA: |
- |
| Biological function: |
promotes trastuzumab resistance; sustains HER2 downstream signaling; increases cell viability and colony formation under trastuzumab; promotes tumor growth under trastuzumab in vivo |
| Molecular mechanism: |
circCDYL2 binds GRB7 and FAK, acts as a scaffold to enhance GRB7/FAK interaction; stabilizes GRB7 protein by inhibiting ubiquitination (involving Pin1), sustaining AKT and ERK1/2 activation |
| Biological pathway or process: |
PI3K/AKT (promotes); ERK (promotes); drug resistance (promotes); ubiquitination (inhibits); proliferation (promotes) |
| Detected method: |
Q
H
S
|
| Validation methods: |
RNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; ISH (In Situ Hybridization); RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Western Blot; IF (Immunofluorescence); Transfection; CCK8; Colony Formation Assay; EdU Staining; In Vivo Animal Model; IHC (Immunohistochemistry); Survival Analysis |
| Clinical significance: |
High circCDYL2 is associated with higher recurrence rate after trastuzumab treatment and shorter DFS and OS; potential biomarker for trastuzumab-resistance in HER2+ BC patients. |
| Description: |
circCDYL2 is up-regulated in trastuzumab-resistant HER2+ breast cancer and promotes resistance in vitro and in vivo. It binds GRB7 and FAK to form a scaffold complex, stabilizes GRB7 by reducing ubiquitination (linked to Pin1), and sustains downstream PI3K/AKT and ERK signaling. High circCDYL2 predicts higher recurrence and poorer DFS/OS after anti-HER2 therapy. |
| Confidence score: |
0.8861 |