RACK1 (Receptor For Activated C Kinase 1)

Consequently, inhibiting the SMYD3-SMAD3 interaction may represent a promising therapeutic strategy for addressing CRC metastasis. In conclusion, targeting the SMYD3-RACK1-SMAD3 transcriptional complex presents a viable approach for the treatment of CRC metastasis.

Deletion of ASC1 enhances a non-canonical form of autophagy that effectively counteracts TDP-43 induced autophagy inhibition despite reduced TOROID formation. Our findings highlight autophagy-not polysome sequestration-as a key mechanism underlying ASC1-mediated modulation of TDP-43 toxicity and suggest autophagy as a promising therapeutic target.

This stabilization leads to RACK1-driven transcriptional activation of key fatty acid metabolic enzymes, enhancing triglyceride synthesis and fueling tumor growth through metabolic reprogramming. Collectively, our study identifies the USP49/RACK1 axis as a critical driver of HCC progression and nominates USP49 as a promising therapeutic target.

This mechanism allows the cell to rapidly reprogram its proteomic landscape in response to stimuli, pivoting between protein synthesis and stress adaptation. Our model resolves the apparent dichotomy of RACK1's roles by framing it as a cellular "resource manager," whose regulated switching between functional states ensures an optimal response to the extracellular environment, with significant implications for understanding cancer and neurodegenerative diseases.

Second- and third-line TKIs, such as sunitinib and regorafenib, provide limited benefits, highlighting the urgent need to address resistance mechanisms. These findings uncover a TGF-β1/CCN2/Rack1/PGK1 mechanism linking CAF-mediated metabolic reprogramming to imatinib resistance in GISTs. Targeting CAF-GIST interactions and key metabolic pathways presents a promising therapeutic strategy.

Furthermore, we identify the natural compound Q3MG as a direct binder of Pro-IL-1β; it promotes lysosomal degradation of Pro-IL-1β and suppresses metastatic progression both in vitro and in vivo. Our study reveals a non-canonical, moonlighting function of Pro-IL-1β in tumor progression and highlights Q3MG as a promising therapeutic agent against metastatic cancer.

These findings indicate that, beyond the canonical GPX4 pathway, the xCT/CD98 complex can inhibit ferroptosis via the TRIM21/RACK1/FPN1 axis. Targeting RACK1 offers a potential therapeutic strategy to sensitize tumors to ferroptosis and overcome therapy resistance across multiple cancer types and in people with cancer.

The in vitro and in vivo functions of the MET inhibitor JNJ-38877605 were investigated...CPNE3 could interact with RACK1 through the VWFA domain and activate MET signalling. These findings may provide new insights into the development of novel therapeutic strategies for NSCLC.

Notably, USP17LA interacts with RACK1 and prevents its ubiquitin-dependent degradation, thereby promoting RACK1-mediated suppression of NFAT activity and the subsequent inhibition of T-cell function. These findings establish USP17LA as a pivotal modulator of T-cell activation and suggest that targeting USP17LA could enhance anti-tumor immunity, offering a potential strategy for cancer immunotherapy.

Catalpol also synergizes with chemotherapeutic and adjuvant agents to induce cancer control, including regorafenib in liver cancer and chloroquine in gastric cancer, promoting increased anticancer action via upregulated cancer cell apoptosis, decreased proliferation, and inhibited angiogenesis via PI3K/p-Akt/mTOR/NF-κB, VEGF/VEGFR2, and Bax signaling pathways modulation. Pyrazole-, imidazole-, and hydrolyzed-based catalpol derivatives increase cancer cell apoptosis and death and decrease tumor angiogenesis through similar pathways. This review seeks to provide understanding of catalpol's anticancer effects, its mechanisms of action, and its potential as a therapeutic anticancer agent while advocating for future research conductance.

Unlike TDP-43, FUS does not inhibit autophagy. These findings highlight autophagy, rather than polysome sequestration, as the key mechanism of TDP-43 toxicity and its mitigation via ASC1/RACK1 reduction.