PRKCB (Protein Kinase C Beta)

Rescue experiments were performed with the MAPK inhibitor trametinib...We reveal a novel oncogenic axis in which MYBL2 and SUMOylation cooperatively increase UBE2C expression and stability, promoting HCC progression via MAPK pathway activation. Targeting the MYBL2/UBE2C/MAPK axis represents a potential therapeutic strategy for treating HCC.

Wavelet-based individualized brain structural networks have been proposed for glioma grading models, resulting in novel imaging and molecular markers for cancer neuroscience.

Notably, elevated PKCβ levels enhance the efficacy of ferroptosis-inducing cancer therapies, while inhibition of the Ca2 +-PKCβ signaling pathway protects against acute pancreatitis by suppressing ferroptosis. These findings underscore the therapeutic potential of targeting Ca2 +-PKCβ-mediated ferroptosis, offering new avenues for the treatment of cancer and acute pancreatitis.

This study systematically characterizes the molecular landscape and features of primary breast tumors and their matched metastatic lymph nodes. These insights enhance our understanding of early-stage breast cancer metastasis and may pave the way for improved diagnostic tools and targeted therapeutic strategies.

By inhibiting PKCβ, MS-553 blocks B-cell receptor signaling and WNT/β-catenin and NF-κB functions, thereby inducing apoptosis in BTK inhibitor-resistant cells. See related article by Gordon et al., p. XX .

(Z)-endoxifen (hereafter endoxifen), the most abundant active tamoxifen metabolite, has emerged as a promising drug candidate due to its superior anti-estrogenic activity and favorable side effect profile...Resistant cells were characterized by stronger inhibition of the estrogen response, partial retention of endoxifen's antiproliferative effects, acquired activation of proinflammatory pathways and epithelial-mesenchymal transition (EMT), activation of the mTOR pathway (contrasting with its inhibition in sensitive cells), and elevated levels of PKCβ. These resistance-specific changes may potentially drive an endoxifen resistance phenotype and, therefore, proteins involved in these pathways may be proposed as potential therapeutic targets for overcoming endoxifen resistance in breast cancer.

These results suggest that the miR-4664-3p/PRKCB axis is crucial in NSCLC progression and immune modulation. Hence, MiR-4664-3p is a potential diagnostic and prognostic indicator, as well as therapeutic target in immunotherapy strategies for NSCLC.

We established and validated a novel MPT-driven necrosis-based prognostic model for SKCM. This model reliably predicted patient outcomes and immune status. BIRC3 emerged as a potential regulator of T-cell dysfunction and a promising therapeutic target in SKCM.

Furthermore, survival analysis revealed that miR-93-5p (HR = 0.72, p = 0.0246), HCC stage (HR = 2.43, p = 0.0000113), TCF4 (HR = 0.66, p = 0.0106), DNAJB4 (HR = 1.29, p = 0.0214), MCC (HR = 1.35, p = 0.0268), and CYB5A (HR = 0.77, p = 0.0423) affect overall survival (OS). Finally, a combined prognostic model for the miRNA cluster and its target genes via the random forest approach revealed that the miR-106b/25 cluster and its interactome are significantly associated with OS (p < 0.0001), thereby providing a comprehensive understanding of the cluster and its targets in the development and progression of HCC and its use as a potential marker for HCC.

MS-553 reduced BCR and Wnt/β-catenin signaling, overcame stromal cell mediated protection, and synergized with venetoclax in CLL samples. Furthermore, MS-553 delayed disease progression and prolonged survival in the Eµ-MTCP1 murine model of CLL. Collectively our results demonstrate that selective inhibition of PKCβ has the potential to overcome BTKi-resistant CLL.

Bioinformatic analysis of mEGFR lung cancers highlighted basal cells, a subtype of lung cell which intrinsically express high PRKCA, as the likely cell-of-origin, suggesting that cell lineage sets a high ceiling for PKCα abundance, while mEGFR licenses the activation of the kinase. Collectively, these data define a pathway-specific role for cPKCs, particularly PKCα, as upstream effectors of mTORC1 in mEGFR systems, establishing a neomorphic dependency on the PKCα-AKT-mTORC1 signaling arm that sustains tumorigenesis via biased signaling by the mutant receptor.