Prognostic value of peptidyl-prolyl cis–trans isomerase 1 (PIN1) in human malignant tumors

Khoei, Saeideh Gholamzadeh; Mohammadi, Chiman; Mohammadi, Younes; Sameri, Saba; Najafi, Rezvan

doi:10.1007/s12094-019-02233-5

Cited by 5 publications

(3 citation statements)

References 44 publications

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“…However, of all the 17 cancer types analyzed, only in two types, renal and pancreatic, are Pin1 expression prognostic: high Pin1 expression is favorable for better prognosis as determined by Human Protein Atlas ( Table 1). This appears to contradict a recent report on the prognostic value of Pin1 in cancer which analyzed the data from 20 published papers (2,474 patients) which concluded that Pin1 overexpression was significantly associated with advanced clinical stage of cancer, lymph node metastasis and poor prognosis, although no correlation with poor differentiation was found (Khoei et al, 2019). Interestingly, it is known that over 50% of cancers have mutations in p53, and Pin1 expression was found to promote mutant p53-induced oncogenesis (Girardini et al, 2011).…”

Section: Cis-atr's Anti-apoptotic Function May Support An Oncogenic Pcontrasting

confidence: 71%

Phosphorylation-Dependent Pin1 Isomerization of ATR: Its Role in Regulating ATR’s Anti-apoptotic Function at Mitochondria, and the Implications in Cancer

Makinwa

Musich

Zou

2020

Front. Cell Dev. Biol.

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Peptidyl-prolyl isomerization is an important post-translational modification of protein because proline is the only amino acid that can stably exist as cis and trans, while other amino acids are in the trans conformation in protein backbones. This makes prolyl isomerization a unique mechanism for cells to control many cellular processes. Isomerization is a rate-limiting process that requires a peptidyl-prolyl cis/trans isomerase (PPIase) to overcome the energy barrier between cis and trans isomeric forms. Pin1, a key PPIase in the cell, recognizes a phosphorylated Ser/Thr-Pro motif to catalyze peptidyl-prolyl isomerization in proteins. The significance of the phosphorylation-dependent Pin1 activity was recently highlighted for isomerization of ATR (ataxia telangiectasia-and Rad3-related). ATR, a PIKK protein kinase, plays a crucial role in DNA damage responses (DDR) by phosphorylating hundreds of proteins. ATR can form cis or trans isomers in the cytoplasm depending on Pin1 which isomerizes cis-ATR to trans-ATR. Trans-ATR functions primarily in the nucleus. The cis-ATR, containing an exposed BH3 domain, is anti-apoptotic at mitochondria by binding to tBid, preventing activation of pro-apoptotic Bax. Given the roles of apoptosis in many human diseases, particularly cancer, we propose that cytoplasmic cis-ATR enables cells to evade apoptosis, thus addicting cancer cells to cis-ATR formation for survival. But in normal DDR, a predominance of trans-ATR in the nucleus coordinates with a minimal level of cytoplasmic cis-ATR to promote DNA repair while preventing cell death; however, cells can die when DNA repair fails. Therefore, a delicate balance/equilibrium of the levels of cis-and trans-ATR is required to ensure the cellular homeostasis. In this review, we make a case that this anti-apoptotic role of cis-ATR supports oncogenesis, while Pin1 that drives the formation of trans-ATR suppresses tumor growth. We offer a potential, novel target that can be specifically targeted in cancer cells, without killing normal cells, to significantly reduce the adverse

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Section: Cis-atr's Anti-apoptotic Function May Support An Oncogenic Pcontrasting

confidence: 71%

Phosphorylation-Dependent Pin1 Isomerization of ATR: Its Role in Regulating ATR’s Anti-apoptotic Function at Mitochondria, and the Implications in Cancer

Makinwa

Musich

Zou

2020

Front. Cell Dev. Biol.

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“…Having chemotactic and inflammatory properties, they play a role as vehicles for eosinophils, basophils and monocytes [ 26 ]. Furthermore, proteins that have PPIase activity, such as the Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1), are shown to be upregulated in various cancers and are considered as prognostic markers and as a therapeutic target [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Interception of Signaling Circuits of Esophageal Adenocarcinoma Cells by Resveratrol Reveals Molecular and Immunomodulatory Signatures

Dhir

Choudhury

Patil

et al. 2021

Cancers

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Deregulation of signaling pathways due to mutations sets the cell on a path to neoplasia. Therefore, recent reports of increased mutations observed in esophageal tissue reflects the enhanced risk of tumor formation. In fact, adenocarcinoma of the esophagus has been on the rise lately. Increase in mortality due to a paucity of efficacious drugs for this cancer prompted us to discover molecular signatures to combat this malady. To this end, we chose resveratrol—a polyphenol with anticancer property—and studied its impact on three esophageal adenocarcinoma cell lines (OE33, OE19 and FLO-1) by multilevel profiling. Here, we show the impact of resveratrol on the viability of the three adenocarcinoma esophageal cell systems studied, at the cellular level. Furthermore, an analysis at the molecular level revealed that the action was through the programmed cell death pathway, resulting in an increase in apoptotic and caspase-positive cells. The impact on reactive oxygen species (ROS) and a decrease in Bcl2 levels were also observed. Moreover, proteomic profiling highlighted pivotal differentially regulated signaling molecules. The phenotypic effect observed in resveratrol-treated esophageal cells could be due to the stoichiometry per se of the fold changes observed in entities of key signaling pathways. Notably, the downregulation of Ku80 and other pivotal entities by resveratrol could be harnessed for chemo-radiation therapy to prevent DNA break repair after radiation therapy. Additionally, multilevel profiling has shed light on molecular and immune-modulatory signatures with implications for discovering novel treatments, including chemo-immunotherapy, for esophageal adenocarcinomas which are known to be aggressive cancers.

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“…It is interesting to note that mutations in p53 are known to occur in more than 50% of cancer types, and Pin1 expression has been shown to support mutant p53-induced oncogenesis [72]. Moreover, Pin1 regulates the wild type p53 function in DDR and also isomerizes it for wild type p53 [97][98][99]. Therefore, the p53 status can have a bearing on the relationship between Pin1 expression and cancer, as there may be different effects for mutant or wild types of p53 in tumor cells [100].…”

Section: The Cis-atr Anti-apoptotic Role Drives Oncogenesis In Dividi...mentioning

confidence: 99%

Novel Cellular Functions of ATR for Therapeutic Targeting: Embryogenesis to Tumorigenesis

Biswas

Makinwa

Zou

2023

IJMS

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The DNA damage response (DDR) is recognized as having an important role in cancer growth and treatment. ATR (ataxia telangiectasia mutated and Rad3-related) kinase, a major regulator of DDR, has shown significant therapeutic potential in cancer treatment. ATR inhibitors have shown anti-tumor effectiveness, not just as monotherapies but also in enhancing the effects of standard chemotherapy, radiation, and immunotherapy. The biological basis of ATR is examined in this review, as well as its functional significance in the development and therapy of cancer, and the justification for inhibiting this target as a therapeutic approach, including an assessment of the progress and status of previous decades’ development of effective and selective ATR inhibitors. The current applications of these inhibitors in preclinical and clinical investigations as single medicines or in combination with chemotherapy, radiation, and immunotherapy are also fully reviewed. This review concludes with some insights into the many concerns highlighted or identified with ATR inhibitors in both the preclinical and clinical contexts, as well as potential remedies proposed.

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Prognostic value of peptidyl-prolyl cis–trans isomerase 1 (PIN1) in human malignant tumors

Cited by 5 publications

References 44 publications

Phosphorylation-Dependent Pin1 Isomerization of ATR: Its Role in Regulating ATR’s Anti-apoptotic Function at Mitochondria, and the Implications in Cancer

Phosphorylation-Dependent Pin1 Isomerization of ATR: Its Role in Regulating ATR’s Anti-apoptotic Function at Mitochondria, and the Implications in Cancer

Interception of Signaling Circuits of Esophageal Adenocarcinoma Cells by Resveratrol Reveals Molecular and Immunomodulatory Signatures

Novel Cellular Functions of ATR for Therapeutic Targeting: Embryogenesis to Tumorigenesis

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