PLK1 (Polo Like Kinase 1)

FAM216A is overexpressed in HCC tissues and is associated with poor clinical outcomes. Mechanistically, FAM216A promotes aggressive tumor behavior by activating the PLK1/ERK signaling pathway.

In vitro experiments showed that the nanoparticles significantly inhibited the proliferation of U87MG glioma cells, induced apoptosis, and specifically silenced the mRNA and protein expression of PLK1. The results of in vivo animal experiments showed that PAPA@siPLK1 could effectively inhibit tumor growth and had potential brain permeability; The PAPA@siPLK1 nanocarrier delivery system developed in this study achieves PLK1 gene silencing through efficient siRNA delivery, providing an important basis for novel therapeutic strategies for glioma.

Collectively, these findings elucidate how targeted kinase loss drives homeostatic signaling networks in cancer cells. By systemically characterizing cellular-level signaling changes and contextualizing them within known kinase pathways, our results provide insights into synthetic lethality and identify potential therapeutic targets to counteract adaptive resistance to kinase inhibitors.

8d also induced cell apoptosis through the mitochondrial pathways, as evidenced by alterations in the expressions of pertinent proteins, including Bcl-2 and Bax. These results indicated that the novel spirotetramine derivative 8d is a potential anti-cancer candidate drug and provides a new structural basis for the development of anti-cancer drugs.

In vitro and in vivo studies demonstrate that the developed nanoparticle exhibits high levels of silencing efficiency, antitumor activity, and therapeutic efficacy. Consequently, this study provides a novel approach to cancer treatment by simultaneously disrupting two stages of tumor cell division.

Our study identified PLK1 as a key regulator of β-catenin signaling flexibility in CRC, coordinating kinase-dependent and transcriptional mechanisms to sustain pathway activation. The discovery of the PLK1-NFKB2-USP2a-β-catenin axis provides a novel therapeutic rationale for targeting PLK1 to selectively disrupt Wnt-driven tumorigenesis, potentially overcoming the toxicity limitations of conventional Wnt inhibitors.

Furthermore, the high risk score was significantly correlated with a 'cold' immune microenviroment, suggesting that acrolein-related genes may modulate the tumor immune microenvironment. Collectively, these findings highlight the role of acrolein in OSCC progression, suggesting the importance of reducing acrolein exposure for cancer prevention and public health, and call for increased attention to the relationship between environmental toxicants and disease initiation, providing a scientific basis for public health interventions and cancer prevention strategies.

In line with this finding, both JAK1 knockout and kinase inhibition with abrocitinib prevented subsequent formation of radiation-induced micronuclei. Targeting the mitotic kinesin KIF18A with the small molecule sovilnesib exacerbated mitotic stress and enhanced the efficacy of radiation. These studies establish KIF18A inhibition as a strategy to counteract the protective G2/M cell cycle arrest induced by DNA damage and to thus enhance tumor cell sensitivity to radiation therapy.

In A549 xenograft models, intravenous administration of siPLK1/bola DS-C6-K4 achieved substantial reductions in tumor growth and PLK1 expression while exhibiting minimal systemic toxicity. This study highlights a synergistic approach utilizing bola-amphiphilic peptide dendrimers for tumor-specific and cytosolic siRNA delivery, leveraging membrane-thiol interactions and intracellular GSH-triggered siRNA release.

Targeted inhibition of YTHDC1/USP10/PLK1 axis may be an effective measure to inhibit EC progression and improve radiosensitivity.

Our study identifies ERCC6L as a novel upstream transcriptional regulator of PLK1 that fuels melanoma progression by reprogramming glucose metabolism. The ERCC6L-PLK1-glycolysis axis represents a promising prognostic biomarker and a potential therapeutic target for cutaneous melanoma.