Prolyl isomerase Pin1 sculpts the immune microenvironment of colorectal cancer

Li, Yang; Yuan, Zhongnan; Wang, Linlin; Yang, Jing; Pu, Pei; Le, Yunting; Chen, XianWei; Wang, Chongyang; Gao, Yating; Liu, Yi; Wang, Jialin; Gao, Xu; Li, Yanze; Wang, Hefei; Zou, Chaoxia

doi:10.1016/j.cellsig.2024.111041

Cited by 2 publications

(1 citation statement)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, Pin1 promotes the lysosomal-mediated degradation of PD-L1; thus, Pin1 inhibition can increase PD-L1 expression ( Koikawa et al, 2021 ). As a result, Pin1 inhibitors synergize with anti-PD-1 therapy in PDAC and colorectal cancer ( Koikawa et al, 2021 ; Li et al, 2024 ). Recent studies suggest that patients with elevated PD-L1 respond better to PD-1 blockade ( Herbst et al, 2014 ).…”

Section: Mechanisms Of Pin1 Dysregulation In Cancermentioning

confidence: 99%

The role of the master cancer regulator Pin1 in the development and treatment of cancer

Stewart,

Sharma,

et al. 2024

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

This review examines the complex role of Pin1 in the development and treatment of cancer. Pin1 is the only peptidyl–prolyl isomerase (PPIase) that can recognize and isomerize phosphorylated Ser/Thr-Pro peptide bonds. Pin1 catalyzes a structural change in phosphorylated Ser/Thr-Pro motifs that can modulate protein function and thereby impact cell cycle regulation and tumorigenesis. The molecular mechanisms by which Pin1 contributes to oncogenesis are reviewed, including Pin1 overexpression and its correlation with poor cancer prognosis, and the contribution of Pin1 to aggressive tumor phenotypes involved in therapeutic resistance is discussed, with an emphasis on cancer stem cells, the epithelial-to-mesenchymal transition (EMT), and immunosuppression. The therapeutic potential of Pin1 inhibition in cancer is discussed, along with the promise and the difficulties in identifying potent, drug-like, small-molecule Pin1 inhibitors. The available evidence supports the efficacy of targeting Pin1 as a novel cancer therapeutic by analyzing the role of Pin1 in a complex network of cancer-driving pathways and illustrating the potential of synergistic drug combinations with Pin1 inhibitors for treating aggressive and drug-resistant tumors.

show abstract

Section: Mechanisms Of Pin1 Dysregulation In Cancermentioning

confidence: 99%

The role of the master cancer regulator Pin1 in the development and treatment of cancer

Stewart,

Sharma,

et al. 2024

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery

Lu,

Zhou

2024

Sci. Signal.

View full text Add to dashboard Cite

Protein phosphorylation is one of the most common mechanisms regulating cellular signaling pathways, and many kinases and phosphatases are proven drug targets. Upon phosphorylation, protein functions can be further regulated by the distinct isomerase Pin1 through cis-trans isomerization. Numerous protein targets and many important roles have now been elucidated for Pin1. However, no tools are available to detect or target cis and trans conformation events in cells. The development of Pin1 inhibitors and stereo- and phospho-specific antibodies has revealed that cis and trans conformations have distinct and often opposing cellular functions. Aberrant conformational changes due to the dysregulation of Pin1 can drive pathogenesis but can be effectively targeted in age-related diseases, including cancers and neurodegenerative disorders. Here, we review advances in understanding the roles of Pin1 signaling in health and disease and highlight conformational regulation as a distinct signal transduction checkpoint in disease development and treatment.

show abstract

Prolyl isomerase Pin1 sculpts the immune microenvironment of colorectal cancer

Cited by 2 publications

References 46 publications

The role of the master cancer regulator Pin1 in the development and treatment of cancer

The role of the master cancer regulator Pin1 in the development and treatment of cancer

Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery

Contact Info

Product

Resources

About