Pin1 promotes prostate cancer cell proliferation and migration through activation of Wnt/β-catenin signaling

Zhu, Z.; Zhang, H.; Lang, Fang; Liu, G.; Dian-jun, Gao; Li, B.; Liu, Y.

doi:10.1007/s12094-015-1431-7

Cited by 25 publications

(21 citation statements)

References 15 publications

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“…This is in agreement with the increased cell proliferation and increased histone acetylation following serum stimulation in wild-type versus PIN1 knockout cells (Supplemental Fig. S4D-F) as well as with published works showing a role for PIN1 and MYC in cell migration (Smith et al 2008;Cho et al 2010;Matsuura et al 2010;Zhao et al 2013;Luo et al 2014;Zhu et al 2016).…”

Section: Myc-gcn5 Localization To the Npc Activates Resident Target Gsupporting

confidence: 92%

Post-translational modification localizes MYC to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals

Pelz

Huang

et al. 2018

Genes Dev.

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The transcription factor MYC (also c-Myc) induces histone modification, chromatin remodeling, and the release of paused RNA polymerase to broadly regulate transcription. MYC is subject to a series of post-translational modifications that affect its stability and oncogenic activity, but how these control MYC's function on the genome is largely unknown. Recent work demonstrates an intimate connection between nuclear compartmentalization and gene regulation. Here, we report that Ser62 phosphorylation and PIN1-mediated isomerization of MYC dynamically regulate the spatial distribution of MYC in the nucleus, promoting its association with the inner basket of the nuclear pore in response to proliferative signals, where it recruits the histone acetyltransferase GCN5 to bind and regulate local gene acetylation and expression. We demonstrate that PIN1-mediated localization of MYC to the nuclear pore regulates MYC target genes responsive to mitogen stimulation that are involved in proliferation and migration pathways. These changes are also present at the chromatin level, with an increase in open regulatory elements in response to stimulation that is PIN1-dependent and associated with MYC chromatin binding. Taken together, our study indicates that post-translational modification of MYC controls its spatial activity to optimally regulate gene expression in response to extrinsic signals in normal and diseased states.

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Section: Myc-gcn5 Localization To the Npc Activates Resident Target Gsupporting

confidence: 92%

Post-translational modification localizes MYC to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals

Pelz

Huang

et al. 2018

Genes Dev.

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“…The results were in accordance with the downregulation of Cyclin D1 and CDK2 in Pin1 knockdown cell groups and CyclinE associated CDK2 kinase activity, which are key regulators of G1/the S phase. In previous studies, Pin1 promotes Cyclin D1 overexpression by activating its promoter or in cooperation with Ras or Wnt/β‐catenin signaling pathways . Furthermore, Pin1 works synergistically with CDK2 in breast cancer or restores CDK2 kinase activity indirectly .…”

Section: Discussionmentioning

confidence: 89%

Pin1 inhibition potently suppresses gastric cancer growth and blocks PI3K/AKT and Wnt/β‐catenin oncogenic pathways

Zhang

Zheng

et al. 2019

Molecular Carcinogenesis

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Gastric cancer is the second leading cause of cancer-related mortality and the fourth most common cancer globally. High intratumor heterogeneity of advanced gastric cancer poses great challenges to targeted therapy due to simultaneous activation of many redundant cancer-driving pathways. A central common signaling mechanism in cancer is prolinedirected phosphorylation, which is further regulated by the unique proline isomerase Pin1.Pin1 inhibition exerts anticancer activity by blocking multiple cancer-driving pathways in some cancers, but its role in gastric cancer is not fully understood. Here we detected Pin1 protein expression in 1065 gastric cancer patients and paired normal tissues using immunohistochemistry and Western blot, and then examined the effects of Pin1 overexpression, and genetic and chemical Pin1 inhibition using Pin1 short hairpin RNA or small molecule inhibitor all-trans retinoic acid (ATRA) on tumorigenesis of human gastric cancer in vitro and in vivo, followed by biochemical analyses to elucidate Pin1 regulated oncogenic pathways. We found that Pin1 was significantly overexpressed in primary and metastasized tumors, with Pin1 overexpression being correlated with advanced stage and poor prognosis. Furthermore, whereas Pin1 overexpression promoted the transformed phenotype in immortalized and nontransformed human gastric cells, either genetic or chemical Pin1 inhibition in multiple human gastric cancer cells potently suppressed cell growth, G1/S transition and colony formation in vitro, as well as tumor growth in xenograft tumor models in vivo, which were further supported by downregulation of multiple key oncoproteins in PI3K/AKT and Wnt/β-catenin signaling pathways. These results not only provide the first evidence for a critical role of Pin1 in the tumorigenesis of gastric cancer but also suggest that targeting Pin1 using ATRA or other inhibitors offers an effective new therapeutic approach for treating advanced gastric cancer.

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“…Phosphorylation of many mitosis‐regulating proteases such as PLK‐11, Cdc25, and Cdc27 depends on Pin1 . Hence, modulation of Pin1 is reported in many processes and diseases ranging from inflammation and differentiation to vascular dysfunction and skin, breast, liver, and prostate cancers . In the present study therefore, we used juglone, an established Pin1 inhibitor, to check if it has any effect on an important process of wound healing in vitro and/or in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…21,22 Hence, modulation of Pin1 is reported in many processes and diseases ranging from inflammation and differentiation to vascular dysfunction and skin, breast, liver, and prostate cancers. 16,[27][28][29][30][31] In the present study therefore, we used juglone, an established Pin1 inhibitor, 32 to Initial studies on this quinone pointed toward its toxicity; 12 however, later and recent researches have brought to light the beneficial effects of juglone in different phenomena and diseases. The cytotoxic and inhibitory effects of juglone have recently been proved to affect tumor and cancer cells more than normal cells, demonstrating its curative property against many types of cancers.…”

Section: Discussionmentioning

confidence: 99%

Juglone ameliorates skin wound healing by promoting skin cell migration through Rac1/Cdc42/PAK pathway

Wahedi

Park

Moon

et al. 2016

Wound Repair Regeneration

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Skin cell regeneration and wound healing are key processes in the recovery from skin injuries. Rapid cell migration and regeneration of skin cells lead to faster and better healing of wounded skin. In the present study, we aimed to investigate the wound healing potential of juglone, a naturally occurring Pin1 inhibitor found in walnuts. Cultured skin cells (NHDF and HaCaT) and hairless mice were treated with juglone after wound creation to examine its effects on cell migration and wound healing rate. The expressions of cell migration related proteins (Rac1, Cdc42, and α-PAK), collagen deposition, and angiogenesis were analyzed. Juglone treatment resulted in faster rate of growth and migration and recovered cell morphology, particularly at a concentration of 5 µM, in skin cells compared to the untreated group. In vivo experiments showed that mice treated with juglone showed faster wound healing rate with better skin morphology and collagen deposition than the vehicle group. Furthermore, juglone increased the activation and/or expression of Cdc42, Rac1, and α-pak in HaCaT cells, and resulted in enhanced angiogenesis in endothelial cells (HUVECs). Juglone also activated MAPKs signaling by activation of ERK, JNK, and p38 proteins. Taken together, these data suggest that juglone may be a potential candidate for wound healing and skin regeneration which ameliorates wound healing mainly by promoting skin cell migration through Rac1/Cdc42/PAK pathway.

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Pin1 promotes prostate cancer cell proliferation and migration through activation of Wnt/β-catenin signaling

Abstract: Our results suggest that Pin1 plays an important role in tumorigenesis of PCa, suggesting that targeting Pin1 pathway could represent a potential modality for treating PCa.

Cited by 25 publications

References 15 publications

Post-translational modification localizes MYC to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals

Post-translational modification localizes MYC to the nuclear pore basket to regulate a subset of target genes involved in cellular responses to environmental signals

Pin1 inhibition potently suppresses gastric cancer growth and blocks PI3K/AKT and Wnt/β‐catenin oncogenic pathways

Juglone ameliorates skin wound healing by promoting skin cell migration through Rac1/Cdc42/PAK pathway

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