TNIK (TRAF2 And NCK Interacting Kinase)

In clinical lung cancer tissue samples, circTNIK expression was positively correlated with GRP78 expression and negatively correlated with IFN-I signaling intensity, further supporting its oncogenic role in vivo. In summary, this study reveals that circTNIK plays a key role in CNTs-induced lung cancer development by regulating GRP78-mediated ER stress and IFN-I immunosuppression, providing a potential biomarker and therapeutic target for the early diagnosis and treatment of environmental-exposure-related lung cancer.

Our findings suggest that TNIK regulates focal adhesion turnover and mitosis to promote tumor malignancy via the RHO/ROCK2/LIMK1 pathway. The combination of TNIK targeting with chemotherapeutic drugs could be an effective strategy to overcome resistance in LUAD.

This identified TNIK, which is modulated by NCB-0846, as a novel target for platinum-resistant HGSC...Our findings identified the TNIK-CDK9 axis as druggable targets mediating platinum resistance and cell viability in HGSC. With AI at the forefront of drug discovery, this work highlights how to ensure that AI findings are biologically relevant by combining compound screens with physiologically relevant models thus supporting the identification and validation of potential drug targets.

The combination of NCB-0846 with cisplatin or etoposide was at best additive. In a subcutaneous xenograft in vivo model, pretreatment with NCB-0846 significantly enhanced the efficacy of IR and caused elevated necrosis in TNIKhigh LK2 tumors but not TNIKlow KNS62 tumors. Overall, these results indicate that TNIK inhibition may be a promising strategy to increase the efficacy of radiotherapy in patients with LSCC with high TNIK expression.

In summary, we proposed a novel regulatory mechanism in which TNIK-mediated cytoskeleton remodeling and cell migration to regulate tumor progression in PTC. TNIK is a therapeutic target in PTC and NCB-0846 would act as a novel targeted drug for PTC therapy.

The combination of NCB-0846 with cisplatin or etoposide was at best additive. In a subcutaneous xenograft in vivo model, pretreatment with NCB-0846 significantly enhanced the efficacy of IR and caused elevated necrosis in TNIKhigh LK2 tumors but not TNIKlow KNS62 tumors. Overall, these results indicate that TNIK inhibition may be a promising strategy to increase the efficacy of radiotherapy in LSCC patients with high TNIK expression.

Our findings unveil a regulatory role of AR as a repressor for TNIK while also highlighting how TNIK activates the EGFR pathway via phosphorylation to drive CRPC progression. Consequently, targeting TNIK may represent an appealing therapeutic strategy for CRPC.

Taken together, LKB1 deficiency promoted CRC cell metastasis via TNIK upregulation and subsequently mediated cytoskeleton remodeling. These results suggest that LKB1-TNIK axis may play a crucial role in CRC progression.

Both TNIK and p-TNIK were upregulated in PTC tissues and p-TNIK was significantly associated with extrathyroidal extension. It may act as a crucial oncogene to participate in PTC carcinogenesis and progression.

Furthermore, our results showed that the Wnt/β-catenin pathway was inhibited by its specific inhibitor XAV-939, but miR-5590-3p inhibitor and adenoviral TNIK overexpression vector (Ad-TNIK) reactivated the activation of Wnt/β-catenin signaling and increased cell malignancy. Lastly, tumorigenicity assay demonstrated that inhibition of miR-5590-3p increased tumor volume and weight in vivo. In conclusion, miR-5590-3p may function as a cancer suppressor gene in OC progression through the Wnt/β-catenin signaling by transcriptionally suppressing TNIK expression, which provides a potential therapeutic approach for ovarian cancer treatment.