PKP1 (Plakophilin 1)

Clinically, PKP1 expression is valuable for cancer subtyping and prognosis. This review also addresses unresolved questions concerning its regulation and suggests that future research in these areas could unlock the potential of PKP1 in precision oncology strategies.

In conclusion, m6A RNA modification may contribute to SKCM metastasis by regulating the expression of CDH3, KRT17, PKP1 and CRABP2, as well as modulating the tumor immune microenvironment. These findings offer novel insights into the metastatic mechanisms of SKCM and identify potential biomarkers for its diagnosis, prognosis and targeted immunotherapy.

Methyl-angolensate, byssochlamic-acid, homoharringtonine, piperacillin and cephaeline were potentially targeted therapeutic compounds for hub genes based on molecular docking. Our study firstly provides new insight into the genetic crosstalk between metastatic melanoma and vitiligo that may facilitate the development of personalized treatments.

These findings highlight a potential therapeutic vulnerability in LUSC metabolic regulation. [Image: see text] The online version contains supplementary material available at 10.1186/s40364-025-00815-w.

In addition, a nomogram was constructed with the prognostic signature and clinical factors, including sex, age and histological grade, and the performance of the nomogram was assessed via calibration plots and decision curve analysis. Thus, our study identified a hypoxia- and immune-related prognostic signature and established a nomogram, which may be helpful for survival prediction in patients with pancreatic cancer.

ROC analysis indicated possible diagnostic value, while Kaplan-Meier plots showed no significant association with survival outcomes. Elevated expression of KRT6A, KRT6B, PKP1, and PKP3 is associated with EC, indicating their potential as candidates for further investigation.

We conclude that the CCND1-PKP1-JUP-ANKRD12 signature may serve as a novel indicator for ESCC prognosis and diagnosis. PKP1 expression might provide new clues for gene therapy efficacy in multiple cancers.

The study contributes to the early prediction of lung cancer by identifying potential biomarkers that could enhance early diagnosis and pave the way for practical clinical applications in the future. Integrating DEGs and machine learning-derived significant genes for PPI analysis offers a robust approach to uncovering critical molecular targets for lung cancer treatment.

Homozygous deletion of PKP1 results in ectodermal dysplasia-skin fragility syndrome (EDSF) and complete knockout of PKP1 in mice produces comparable symptoms to EDSF in humans, although mice do not survive more than 24 h. PKP1 is not limited to expression in desmosomal structures, but is rather widely expressed in cytoplasm and nucleus, where it assumes important cellular functions. This review will summarize distinct roles of PKP1 in the cell membrane, cytoplasm, and nucleus with an overview of relevant studies on its function in diverse types of cancer.

Finally, in silico experiments provided additional information on the possible structure of the binding complex, especially on the binding ARM-PKP1 hot-spot. Our findings suggest that RYBP might be a rescuer of the high expression of PKP1 in tumors, where it could decrease the epithelial-mesenchymal transition in some cancer cells.

In vitro experiments showed that the knockdown of PKP1 inhibited ESCC cell proliferation and migration. These findings suggest that the novel HPRscore and PKP1 may serve as prognostic tools and therapeutic targets for ESCC patients.

Plakophilin 1 (PKP1) was observed to be crucial to the immune microenvironment and has significant effects on melanoma cell proliferation, migration, invasion, and the cell cycle. This signature demonstrates high reliability and has potential for clinical applications.