PTEN Mouse Models of Cancer Initiation and Progression

Lee, Yu-Ru; Pandolfi, Pier Paolo

doi:10.1101/cshperspect.a037283

Cited by 17 publications

(13 citation statements)

References 65 publications

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“…This is also the primary carcinogenic effector of the PI3K/Akt pathway. The phosphatase and the tensin homolog (PTEN) are mainly associated with the dephosphorylation of PIP3 (Lee and Pandolfi, 2020;Chauhan et al, 2021). All mentioned above are Akt's the main negative regulators.…”

Section: Downstream Target Akt Of Pi3kmentioning

confidence: 99%

Research Progress on the Regulation Mechanism of Key Signal Pathways Affecting the Prognosis of Glioma

Wei

et al. 2022

Front. Mol. Neurosci.

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As is known to all, glioma, a global difficult problem, has a high malignant degree, high recurrence rate and poor prognosis. We analyzed and summarized signal pathway of the Hippo/YAP, PI3K/AKT/mTOR, miRNA, WNT/β-catenin, Notch, Hedgehog, TGF-β, TCS/mTORC1 signal pathway, JAK/STAT signal pathway, MAPK signaling pathway, the relationship between BBB and signal pathways and the mechanism of key enzymes in glioma. It is concluded that Yap1 inhibitor may become an effective target for the treatment of glioma in the near future through efforts of generation after generation. Inhibiting PI3K/Akt/mTOR, Shh, Wnt/β-Catenin, and HIF-1α can reduce the migration ability and drug resistance of tumor cells to improve the prognosis of glioma. The analysis shows that Notch1 and Sox2 have a positive feedback regulation mechanism, and Notch4 predicts the malignant degree of glioma. In this way, notch cannot only be treated for glioma stem cells in clinic, but also be used as an evaluation index to evaluate the prognosis, and provide an exploratory attempt for the direction of glioma treatment. MiRNA plays an important role in diagnosis, and in the treatment of glioma, VPS25, KCNQ1OT1, KB-1460A1.5, and CKAP4 are promising prognostic indicators and a potential therapeutic targets for glioma, meanwhile, Rheb is also a potent activator of Signaling cross-talk etc. It is believed that these studies will help us to have a deeper understanding of glioma, so that we will find new and better treatment schemes to gradually conquer the problem of glioma.

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Section: Downstream Target Akt Of Pi3kmentioning

confidence: 99%

Research Progress on the Regulation Mechanism of Key Signal Pathways Affecting the Prognosis of Glioma

Wei

et al. 2022

Front. Mol. Neurosci.

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“…The tumor suppressor gene PTEN has been extensively associated with prostate cancer development and progression [2–4,6–9]. Metabolic changes also occur during prostate tumorigenesis, including alterations in de novo lipogenesis [37,47,48]. Increased levels of FASN are observed in the early phase of prostatic carcinogenesis and its overexpression is associated with poor prognosis, metastasis, and chemoresistance [21,26,28,29,49,50].…”

Section: Discussionmentioning

confidence: 99%

“…Lymph node metastases occur in 45% and lung metastases in 27% of the mice [35]. Overexpression of FASN and altered metabolism in prostate cancer cells are associated with inactivation of PTEN [28,36,37]; in contrast, PTEN expression is inversely correlated with FASN expression in prostate cancer [38], while inhibition of PTEN leads to the overexpression of FASN in vitro . Here, we characterize the role of FASN inactivation in modulating the invasive propensity of PTEN knockout (KO) in a genetically engineered modified mouse (GEMM) model.…”

Section: Introductionmentioning

confidence: 99%

Genetic ablation of FASN attenuates the invasive potential of prostate cancer driven by Pten loss

Bastos

Ribeiro

Ahearn

et al. 2020

The Journal of Pathology

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Loss of the tumor suppressor gene Pten in murine prostate recapitulates human carcinogenesis and causes stromal proliferation surrounding murine prostate intraepithelial neoplasia (mPIN), which is reactive to microinvasion. In turn, invasion has been shown to be regulated in part by de novo fatty acid synthesis in prostate cancer. We therefore investigated the effects of genetic ablation of Fasn on invasive potential in prostate‐specific Pten knockout mice. Combined genetic ablation of Fasn and Pten reduced the weight and volume of all the prostate lobes when compared to single knockouts. The stromal reaction to microinvasion and the cell proliferation that typically occurs in Pten knockout were largely abolished by Fasn knockout. To verify that Fasn knockout indeed results in decreased invasive potential, we show that genetic ablation and pharmacologic inhibition of FASN in prostate cancer cells significantly inhibit cellular motility and invasion. Finally, combined loss of PTEN with FASN overexpression was associated with lethality as assessed in 660 prostate cancer patients with 14.2 years of median follow‐up. Taken together, these findings show that de novo lipogenesis contributes to the aggressive phenotype induced by Pten loss in murine prostate and targeting Fasn may reduce the invasive potential of prostate cancer driven by Pten loss. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.

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“…Like many other tumor suppressor genes, PTEN is frequently dysregulated in cancers by genetic mutations (loss of function) and other molecular mechanisms, including downregulation of gene transcription and posttranslational modifications, leading to downregulation or even loss of protein expression and function. The roles of PTEN in tumor progression and metastasis have been studied in mice with tissue‐specific deletion of PTEN [ 21 ]. For example, conditional deletion of PTEN in lung respiratory epithelial cells of bigenic mice containing both floxed PTEN alleles and a Cre recombinase transgene driven by a club cell secretory protein gene promoter (CCSP‐Cre) caused bronchiolar hyperplasia [ 22 ], implying that another molecular alteration is required for lung tumor development within the context of PTEN loss.…”

Section: Introductionmentioning

confidence: 99%

Conditional ERK3 overexpression cooperates with PTEN deletion to promote lung adenocarcinoma formation in mice

et al. 2021

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ERK3, officially known as mitogen-activated protein kinase 6 (MAPK6), is a poorly studied mitogen-activated protein kinase (MAPK). Recent studies have revealed the upregulation of ERK3 expression in cancer and suggest an important role for ERK3 in promoting cancer cell growth and invasion in some cancers, in particular lung cancer. However, it is unknown whether ERK3 plays a role in spontaneous tumorigenesis in vivo. To determine the role of ERK3 in lung tumorigenesis, we created a conditional ERK3 transgenic mouse line in which ERK3 transgene expression is controlled by Cre recombinase. By crossing these transgenic mice with a mouse line harboring a lung tissue-specific Cre recombinase transgene driven by a club cell secretory protein gene promoter (CCSP-iCre), we have found that conditional ERK3 overexpression cooperates with phosphatase and tensin homolog (PTEN) deletion to induce the formation of lung adenocarcinomas (LUADs). Mechanistically, ERK3 overexpression stimulates activating phosphorylations of erb-b2 receptor tyrosine kinases 2 and 3 (ERBB2 and ERBB3) by upregulating Sp1 transcription factor (SP1)-mediated gene transcription of neuregulin 1 (NRG1), a potent ligand for ERBB2/ERBB3. Our study has revealed a bona fide tumorpromoting role for ERK3 using genetically engineered mouse models. Together with previous findings showing the roles of ERK3 in cultured cells and in a xenograft lung tumor model, our findings corroborate that ERK3 acts as an oncoprotein in promoting LUAD development and progression.

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PTEN Mouse Models of Cancer Initiation and Progression

Cited by 17 publications

References 65 publications

Research Progress on the Regulation Mechanism of Key Signal Pathways Affecting the Prognosis of Glioma

Research Progress on the Regulation Mechanism of Key Signal Pathways Affecting the Prognosis of Glioma

Genetic ablation of FASN attenuates the invasive potential of prostate cancer driven by Pten loss

Conditional ERK3 overexpression cooperates with PTEN deletion to promote lung adenocarcinoma formation in mice

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