Expression of PRIP, a phosphatidylinositol 4,5-bisphosphate binding protein, attenuates PI3K/AKT signaling and suppresses tumor growth in a xenograft mouse model

Maetani, Yuka; Asano, Shigetaka; Mizokami, Akinari; Yamawaki, Yosuke; Sano, Tomomi; Hirata, Masato; Irifune, Masahiro; Kanematsu, Takashi

doi:10.1016/j.bbrc.2021.03.045

Cited by 8 publications

(6 citation statements)

References 23 publications

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“…For further analysis two candidates were selected from this list. First, PLCL1, as this protein is known to be involved in inhibition of tumor growth [ 38 ] and metastasis [ 39 ]. Second, SERPINB6, as serpin activity was one gene ontology class enriched in GSEA, and because SERPINB6 [ 40 ] inhibits metastasis and tumor progression.…”

Section: Resultsmentioning

confidence: 99%

“…Phospholipase C Line 1 (PLCL1) was chosen, as its published functions suggest a role in metastasis. PLCL1 is a catalytically inactive protein binding PI(4,5)P2, thus functioning as a decoy for PI3K, impairing PI3K/AKT signaling and reducing tumor growth [ 38 ]. Concomitantly, PLCL1 inhibits polymerization of actin via PI(3,4,5)P3-WAVE2, thus impairing cell migration [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

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CHD5 inhibits metastasis of neuroblastoma

et al. 2021

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CHD5, a tumor suppressor at 1p36, is frequently lost or silenced in poor prognosis neuroblastoma (NB) and many adult cancers. The role of CHD5 in metastasis is unknown. We confirm that low expression of CHD5 is associated with stage 4 NB. Forced expression of CHD5 in NB cell lines with 1p loss inhibited key aspects of the metastatic cascade in vitro: anchorage-independent growth, migration, and invasion. In vivo, formation of bone marrow and liver metastases developing from intravenously injected NB cells was delayed and decreased by forced CHD5 expression. Genome-wide mRNA sequencing revealed reduction of genes and gene sets associated with metastasis when CHD5 was overexpressed. Known metastasis-suppressing genes preferentially upregulated in CHD5-overexpressing NB cells included PLCL1. In patient NB, low expression of PLCL1was associated with metastatic disease and poor survival. Knockdown of PLCL1 and of p53 in IMR5 NB cells overexpressing CHD5 reversed CHD5-induced inhibition of invasion and migration in vitro. In summary, CHD5 is a metastasis suppressor in NB.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CHD5 inhibits metastasis of neuroblastoma

et al. 2021

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“…7 Maetani et al revealed that using a PI3K inhibitor reduces proliferation by suppressing cyclin D1 expression in human cancer xenografts. 68 Furthermore, inactivation of PI3K-mTOR promotes apoptosis in the breast cancer cell line HER2. 69 The activation of Bcl-2, an antiapoptotic gene, together with the inactivation of Bax, a pro-apoptotic gene, leads to PI3K/AKT pathway activation and was reported to inhibit apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Targeting the PI3K/pAKT/mTOR/NF‐κB/FOXO3a signaling pathway for suppressing the development of hepatocellular carcinoma in rats: Role of the natural remedic Suaeda vermiculata forssk

Abdel‐Bakky,

Mohammed,

Mahmoud

et al. 2024

Environmental Toxicology

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Liver malignancy is well recognized as a prominent health concern, with numerous treatment options available. Natural products are considered a renewable source, providing inspiring chemical moieties that could be used for cancer treatment. Suaeda vermiculata Forssk has traditionally been employed for management of hepatic conditions, including liver inflammation, and liver cirrhosis, as well as to improve general liver function. The findings of our earlier study demonstrated encouraging in vivo hepatoprotective benefits against liver injury generated by paracetamol and carbon tetrachloride. Additionally, Suaeda vermiculata Forssk exhibited cytotoxic activities in vitro against Hep‐G2 cell lines and cell lines resistant to doxorubicin. The present investigation aimed to examine the potential in vivo hepatoprotective efficacy of Suaeda vermiculata Forssk extract (SVE) against hepatocellular carcinoma induced by diethylnitrosamine (DENA) in rats. The potential involvement of the PI3K/AKT/mTOR/NF‐κB pathway was addressed. Sixty adult male albino rats were allocated into five groups randomly (n = 10). First group received a buffer, whereas second group received SVE only, third group received DENA only, and fourth and fifth groups received high and low doses of SVE, respectively, in the presence of DENA. Liver toxicity and tumor markers (HGFR, p‐AKT, PI3K, mTOR, NF‐κB, FOXO3a), apoptosis markers, and histopathological changes were analyzed. The current results demonstrated that SVE inhibited PI3K/AKT/mTOR/NF‐κB pathway as well as increased expression of apoptotic parameters and FOXO3a levels, which were deteriorated by DENA treatment. Furthermore, SVE improved liver toxicity markers and histopathological changes induced by DENA administration. This study provided evidence for the conventional hepatoprotective properties attributed to SV and investigated the underlying mechanism by which its extract, SVE, could potentially serve as a novel option for hepatocellular carcinoma (HCC) treatment derived from a natural source.

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“…Moreover, CYTL1 might serve as a tumor suppressor with broad inhibitory effects on tumor metastasis and the phosphorylation of STAT3 in multiple tumor models (44). Phospholipase C-like 1 (PLCL1), which is homologous to the PLC family, is associated with tumor growth suppression (45) and metastasis (46). The downregulation of PLCL1 expression in clear cell renal carcinoma and neuroblastoma was found to be predictive of poor prognosis (47,48).…”

Section: Discussionmentioning

confidence: 99%

Development of a novel autophagy-related gene model for gastric cancer prognostic prediction

Xu²,

Hu³

et al. 2022

Front. Oncol.

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Gastric cancer (GC) is a major global health issue and one of the leading causes of tumor-associated mortality worldwide. Autophagy is thought to play a critical role in the development and progression of GC, and this process is controlled by a set of conserved regulators termed autophagy-related genes (ATGs). However, the complex contribution of autophagy to cancers is not completely understood. Accordingly, we aimed to develop a prognostic model based on the specific role of ATGs in GC to improve the prediction of GC outcomes. First, we screened 148 differentially expressed ATGs between GC and normal tissues in The Cancer Genome Atlas (TCGA) cohort. Consensus clustering in these ATGs was performed, and based on that, 343 patients were grouped into two clusters. According to Kaplan–Meier survival analysis, cluster C2 had a worse prognosis than cluster C1. Then, a disease risk model incorporating nine differentially expressed ATGs was constructed based on the least absolute shrinkage and selection operator (LASSO) regression analysis, and the ability of this model to stratify patients into high- and low-risk groups was verified. The predictive value of the model was confirmed using both training and validation cohorts. In addition, the results of functional enrichment analysis suggested that GC risk is correlated with immune status. Moreover, autophagy inhibition increased sensitivity to cisplatin and exacerbated reactive oxygen species accumulation in GC cell lines. Collectively, the results indicated that this novel constructed risk model is an effective and reliable tool for predicting GC outcomes and could help with individual treatment through ATG targeting.

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Expression of PRIP, a phosphatidylinositol 4,5-bisphosphate binding protein, attenuates PI3K/AKT signaling and suppresses tumor growth in a xenograft mouse model

Cited by 8 publications

References 23 publications

CHD5 inhibits metastasis of neuroblastoma

CHD5 inhibits metastasis of neuroblastoma

Targeting the PI3K/pAKT/mTOR/NF‐κB/FOXO3a signaling pathway for suppressing the development of hepatocellular carcinoma in rats: Role of the natural remedic Suaeda vermiculata forssk

Development of a novel autophagy-related gene model for gastric cancer prognostic prediction

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