Targeting the PI3K/AKT/mTOR pathway in biliary tract cancers: A review of current evidences and future perspectives

Corti, Francesca; Nichetti, Federico; Raimondi, Alessandra; Niger, Monica; Prinzi, Natalie; Torchio, Martina; Tamborini, Elena; Perrone, Federica; Pruneri, Giancarlo; Bartolomeo, Maria Di; Braud, Filippo de; Pusceddu, Sara

doi:10.1016/j.ctrv.2018.11.001

Cited by 94 publications

(67 citation statements)

References 95 publications

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“…Our experiment revealed that SPOCK1 enhances the activity of the PI3K/Akt pathway, a crucial signaling pathway that promotes cell proliferation, 17 induces the EMT, [18][19][20] and attenuates cell apoptosis by stimulating the Bax-mediated signaling pathway. Our experiment revealed that SPOCK1 enhances the activity of the PI3K/Akt pathway, a crucial signaling pathway that promotes cell proliferation, 17 induces the EMT, [18][19][20] and attenuates cell apoptosis by stimulating the Bax-mediated signaling pathway.…”

Section: Discussionmentioning

confidence: 79%

A potential prognostic marker and therapeutic target: SPOCK1 promotes the proliferation, metastasis, and apoptosis of pancreatic ductal adenocarcinoma cells

Jin

Fang

et al. 2019

J of Cellular Biochemistry

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Pancreatic ductal adenocarcinoma (PDAC), a common malignancy originated from the digestive system worldwide, has a poor clinical outcome. SPOCK1 is a widely investigated member of the Ca2+‐binding proteoglycan family and functions as an essential driver in several cancers. However, the complex regulatory role of SPOCK1 in PDAC is unclear. Bioinformatics analysis predicted an interrelationship between increased SPOCK1 expression and the clinical characteristics of patients with PDAC. The SPOCK1 expression levels in fresh tissue samples were confirmed, and SPOCK1 expression was then knocked down by lentivirus‐mediated short hairpin RNA. Cell proliferation, metastasis, and apoptosis were detected through Cell Counting Kit‐8, colony formation assays, invasion and migration assays, flow cytometric analysis, quantitative real‐time polymerase chain reaction, and Western blot experiment. On the basis of the Cancer Genome Atlas database, we found a significantly higher level of SPOCK1 in PDAC than in adjacent nontumor tissues. Patients with PDAC with high SPOCK1 expression exhibited shorter overall survival time, as well as disease‐free survival time. The knockdown of SPOCK1 significantly decreased the proliferation and metastasis of PCNA‐1 and MIA PaCa‐2 cells. Moreover, the knockdown of SPOCK1 led to cell cycle arrest in G0/G1 phase and increased the proportion of apoptotic PDAC cells by regulating members of the caspase and Bcl‐2 families. Our data proved that SPOCK1 is a critical regulator of tumor proliferation and metastasis in PDAC cells. Therefore, SPOCK1 might be a potential prognostic and therapeutic target molecule in PDAC.

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Section: Discussionmentioning

confidence: 79%

A potential prognostic marker and therapeutic target: SPOCK1 promotes the proliferation, metastasis, and apoptosis of pancreatic ductal adenocarcinoma cells

Jin

Fang

et al. 2019

J of Cellular Biochemistry

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“…The PI3K/AKT/mTOR pathway is a classical signaling pathway playing a vital role in regulating cell growth, apoptosis, cell cycle, metastasis, and other cell biology processes in various cancer types, including GC . Once active, AKT regulates cell proliferation and tumor progression by phosphorylating a variety of downstream cell cycle‐related and antiapoptotic proteins as well as transcription factors .…”

Section: Discussionmentioning

confidence: 99%

Anthrax toxin receptor 1/tumor endothelial marker 8 promotes gastric cancer progression through activation of the PI3K/AKT/mTOR signaling pathway

et al. 2020

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Anthrax toxin receptor 1 (ANTXR1), a type I transmembrane protein, is one of the receptors that facilitates the entrance of anthrax toxin into cells. Previous studies have confirmed the pivotal role of ANTXR1 in progression and tumorigenesis of diverse cancer types. However, the biological function of ANTXR1 in gastric cancer (GC) is still unknown. The present study aimed to investigate the role of ANTXR1 in GC and illuminate the potential molecular mechanisms. Bioinformatics analysis found that ANTXR1 expression was significantly upregulated in GC tissue and its overexpression was associated with poor prognosis of GC patients. Moreover, we confirmed the upregulation of ANTXR1 in GC cell lines and GC tissue by quantitative PCR, western blot analysis, and immunohistochemical analysis. Additionally, high protein expression level of ANTXR1 was positively associated with several clinicopathological parameters in GC patients. In our study, a series of in vitro and in vivo assays were undertaken through strategies of loss/gain-of-function and rescue assays.Consequently, our results indicated that ANTXR1 induced proliferation, cell cycle progression, invasion and migration, and tumorigenicity and induced suppressed apoptosis in GC. Mechanistic investigation indicated that ANTXR1 exerted its promoting effects on GC through activation of the PI3K/AKT/mTOR signaling pathway. In conclusion, our findings suggested that ANTXR1 plays a crucial role in the development and progression of GC and could serve as a novel prognostic biomarker and potential therapeutic target for GC. K E Y W O R D S ANTXR1, EMT, gastric cancer, metastasis, proliferation | 1133 CAI et Al.

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“…1,20 The Akt/mTOR pathway regulates all critical phases of cell growth, including proliferation, differentiation, and apoptosis, and deregulation of this pathway has been reported in several types of tumours. 8,13,14,21,22 The oncogenic role of aberrant Akt/mTOR signalling pathway activation has been investigated in sarcoma. 11,23 However, few previous studies from the Chinese population have focused on synovial sarcomas.…”

Section: Discussionmentioning

confidence: 99%

<p>Impact of the Activation Status of the Akt/mTOR Signalling Pathway on the Clinical Behaviour of Synovial Sarcoma: Retrospective Analysis of 174 Patients at a Single Institution</p>

Li¹,

Ding²,

Wen³

et al. 2020

CMAR

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Phosphoinositide 3-kinase (PI3K) and the downstream Akt/mammalian target of rapamycin (mTOR) pathway are central to the control of cell proliferation and survival. Although abnormal activation of this pathway has been well established in a variety of tumours, limited studies are available on synovial sarcoma. The aim of this study was to investigate the expression of several key proteins of those pathways in synovial sarcomas and to correlate the expression of these proteins with clinicopathologic features and prognosis. Patients and Methods: A total of 174 patients with synovial sarcomas were recruited for this study. The phosphorylation status of Akt, mTOR, and eukaryotic translation initiation factor 4E binding protein (4E-BP1) was measured by immunohistochemistry assays in formalin-fixed, paraffin-embedded samples. Correlations between the expression levels of these proteins and clinicopathologic features and prognosis were analysed. Results: The positive rates of phosphorylated (p)Akt, pmTOR, p4E-BP1, and CyclinD1 were 62.7%, 55.6%, 47.1%, and 52.6%, respectively. The positive results of pmTOR, pAkt, and downstream p4E-BP1 were correlated with each other. The positive pAkt, pmTOR, p4E-BP1, and CyclinD1 results were more highly expressed in head and neck and visceral tumours, and positive p4E-BP1 results were correlated with larger size and larger areas of necrosis. In multivariate analysis of clinicopathologic factors, head and neck and visceral location, large tumour size, larger areas of necrosis and frequent mitosis were confirmed as risk factors for shorter overall survival. Positive pAkt, pmTOR and p4E-BP1 results were correlated significantly with shorter overall survival, and CyclinD1 was not in the univariate analysis. The positive pmTOR, pAkt, p4E-BP1, and CyclinD1 results were significantly poor prognostic factors for overall survival, and only positive p4E-BP1 results were significantly associated with shorter event-free survival in multivariate analysis. Conclusion: This study demonstrated the high expression of pAkt, pmTOR, and p4E-BP1 associated with aggressive clinical behaviour in synovial sarcomas and provided evidence for prognostic evaluation and targeted therapy.

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Targeting the PI3K/AKT/mTOR pathway in biliary tract cancers: A review of current evidences and future perspectives

Cited by 94 publications

References 95 publications

A potential prognostic marker and therapeutic target: SPOCK1 promotes the proliferation, metastasis, and apoptosis of pancreatic ductal adenocarcinoma cells

A potential prognostic marker and therapeutic target: SPOCK1 promotes the proliferation, metastasis, and apoptosis of pancreatic ductal adenocarcinoma cells

Anthrax toxin receptor 1/tumor endothelial marker 8 promotes gastric cancer progression through activation of the PI3K/AKT/mTOR signaling pathway

<p>Impact of the Activation Status of the Akt/mTOR Signalling Pathway on the Clinical Behaviour of Synovial Sarcoma: Retrospective Analysis of 174 Patients at a Single Institution</p>

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