AJUBA (Ajuba LIM Protein)

CuHL1 exhibits potent cytotoxicity in the low micromolar range (IC50 ≈ 2 µM), surpassing cisplatin by up to 81-fold...Functional assays confirm reduced migratory capacity in MDA-MB-231 cells. These findings position CuHL1 as a promising candidate for TNBC therapy, meriting further in vivo evaluation.

Mechanistically, the YAP can accumulate and hyperactivate the super-enhancer of the spindle assembly checkpoint, AJUBA, in a phase-separation-dependent manner, thus leading to aberrant mitosis. These findings reveal a crucial biological role of YAP-mediated super enhancer activation and provide new insights into aneuploidy formation in breast cancer.

Our study identified that NSUN7 regulates key oncogenic pathways associated with tamoxifen resistance and metastasis. Its suppression enhanced tamoxifen sensitivity and reduced metastatic potential, collectively highlighting NSUN7 as a novel driver of tamoxifen resistance and a potent therapeutic target in estrogen receptor-positive breast cancer.

In summary, FER could serve as a prognostic indicator and therapeutic target in DLBCL. Additionally, the application of exosomes in diagnosis or treatment may open up novel avenues for cancer therapy.

Conversely, the S163A mutant significantly attenuates the ubiquitination level of Ajuba. Overall, our study reveals a novel regulatory mechanism of Ajuba at post-translational level and sheds light on the role of GSK3β-β-TrCP axis in the turnover of Ajuba in CRC.

Additionally, the MYBL2-AJUBA axis enhances the migration and invasion of HTR-8/SVneo cells by suppressing the Hippo signaling pathway. Our study indicates that the dysregulation of MYBL2 expression in placental trophoblasts is associated with the pathogenesis of RSA, highlighting its potential as a therapeutic target for this condition.

In conclusion,, overexpression of AJUBA facilitates the proliferation and motility of NSCLC cells via the ERK and Wnt/β-catenin pathways. AJUBA may be useful as a prognostic marker which may provide a promising approach for the treatment of NSCLC.

Importantly, the inhibition of Notch signaling using a small-molecule inhibitor significantly suppressed JUB-induced chemoresistance. Results suggest that JUB plays an important role and may serve as a biomarker for the clinical treatment of patients with 5-FU-resistant colon cancer.

Our findings underlined novel differences in somatic gene mutations among the four anatomic sites. However, at present, the identified mutations cannot yet be considered predictive biomarkers either for the lack of supporting clinical findings or for the lack of approved targeted therapies in HNSCC. This underscores the imperative for continued investigation into the biology of HNSCC to unveil novel vulnerabilities that can be leveraged to enhance patient treatment strategies.

We show that both knockdown of USP7 or Ajuba results in a substantial reduction of cell-cell adhesion, with concomitant effects on other proteins associated with adherens junctions. Our findings underlie the role of USP7 in colorectal cancer through its protein interaction networks and show that the Ajuba protein is a component of USP7 protein networks present in colorectal cancer.

Analysis of a pancancer CRISPR screen database (DepMap) revealed co-dependencies between YAP/TEAD and the P-body core genes and correlations between the mRNA levels of SAMD4A, AJUBA, WTIP, PNRC1, and YAP target genes. Our study suggests that the P-body is a new downstream effector of YAP/TAZ, which implies that reexpression of PNRC1 or disruption of P-bodies is a potential therapeutic strategy for tumors with active YAP.

In conclusion, EHF is upregulated by the CRC and promotes GEA malignancy by interacting with AJUBA through the KRAS pathway. Targeting of both EHF and its coactivator AJUBA through lipid nanoparticles is a novel potential therapeutic strategy.