NEK2 (NIMA Related Kinase 2)

Aberrant expression of Nek2 and Hec1 may contribute to ATL pathogenesis.

However, challenges remain in developing selective, clinically viable agents. This review provides details on the molecular architecture of NEK2, disease mechanisms, and therapeutic potential, framing it as a dual regulator and guardian of mitosis that has become a rogue oncogene and advocating its exploitation in translational medicine across cancer and non-cancer pathologies.

Overall, these results reveal a crucial role of TUFT1 in the regulation of tumor progression through centrosome number control. Thus, TUFT1 represents a promising target for diagnostic and therapeutic approaches for cancers.

USP7 promoted the progression of FTC and induced sorafenib resistance by enhancing NEK2/ATG5-mediated autophagy. This study provides novel insights and potential therapeutic strategies for FTC treatment and overcoming drug resistance.

Inhibition of this pathway with rapamycin resulted in higher cytotoxicity to CRC cells with ZNF695 overexpression, suggesting that elevated ZNF695 levels may increase the sensitivity of CRC cells to rapamycin. In summary, the current study identified ZNF695 as a tumor‑promoting protein in CRC through activation of the NEK2 and PI3K/Akt/mTOR signaling pathways. Targeting the NEK2 and PI3K/Akt/mTOR signaling pathways may therefore be a promising strategy for the treatment of patients with CRC and high ZNF695 expression.

The S1P produced by NEK2hi TAMs promotes hepatic tumor progression and confers immunotherapy resistance. Targeting S1P synthesis with a NEK2 inhibitor or S1P antagonist disrupted the immunosuppressive function of macrophages, shifted regulatory T cells (Tregs) to TH17 cells, and increased the number and activity of tumor-infiltrating T effectors, thereby enhancing antitumor efficacy in synergy with immune checkpoint blockade therapy.

These findings highlight NEK2's essential role in regulating testicular descent and spermatogenesis, implicating it as a potential target for cryptorchidism.

FOXA1 can target the promoter region that binds to NEK2, and it can activate NEK2 through transcription to promote DNA damage repair and cisplatin resistance in cisplatin-resistant LUAD cells. This study confirms that FOXA1 can target NEK2 to promote DNA damage repair and cisplatin resistance in LUAD cells, providing a new valuable therapeutic target for the treatment of LUAD and the control of chemotherapy drug resistance.

In summary, NEK2 promotes cell survival and decreases sensitivity to 5-FU in CRC by activating the Wnt/β-catenin signaling pathway. Consequently, NEK2 holds promise as a potential therapeutic target for CRC management.

NEK2 knockdown significantly suppressed proliferation, migration, and invasion; enhanced cisplatin sensitivity (reduced the IC50); and promoted apoptosis...This study revealed that NEK2 promotes osteosarcoma proliferation, invasion, migration, and chemoresistance while inhibiting apoptosis, likely through AKT/p-AKT signaling. These effects may be regulated by FoxM1.

We demonstrated for the first time that NEK2 is a potential regulator of PASMCs function. Targeting NEK2 may be an effective strategy for the treatment of CHD-PAH.

Moreover, we found a positive correlation between the efficacy of the NEK2 inhibitor INH6 and NEK2 expression levels in ESCC. In conclusion, our findings position NEK2 as a time-dependent oncogene and a potential biomarker in ESCC, highlighting its role in both tumorigenesis and the circadian rhythm.