S6 ribosomal protein phosphorylation is associated with malignancy of intraductal papillary mucinous neoplasm of the pancreas

Hirashita, Teijiro; Hirashita, Yuka; Iwashita, Yukio; Endo, Yuichi; Kiyonaga, Maki; Matsumoto, Shunro; Hijiya, Naoki; Moriyama, Masatsugu; Murakami, Kazunari; Ito, Masafumi

doi:10.1002/ags3.12367

Cited by 13 publications

(11 citation statements)

References 30 publications

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“…In the present study, the expression of GLUT-1 on immunohistochemical staining was almost nonexistent or weak among the HGD group, in which FDG uptake was low, whereas it was strong for the INV group, with its high FDG uptake. Hirashita et al evaluated GLUT-1 and FDG-PET/CT using 39 IPMN pancreatic resection specimens, and found that the expression of GLUT-1 was significantly higher in carcinoma than in adenoma, showing that there is a correlation between SUV-max and the expression of GLUT-1 [ 37 ]. Oda et al reported that HGD and INV showed higher expression of GLUT-1 than LGD [ 38 ]; their studies also found that there are tissue subtypes of IPMN, including many oncocytic types ( n = 7) and the pancreatobiliary type ( n = 21), which have higher expression of GLUT-1 than those seen in the gastric type ( n = 30) and intensive type ( n = 22).…”

Section: Discussionmentioning

confidence: 99%

Clinical Utility and Limitation of Diagnostic Ability for Different Degrees of Dysplasia of Intraductal Papillary Mucinous Neoplasms of the Pancreas Using 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography

Hozaka

Kurahara

et al. 2021

Cancers

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The diagnostic value of 18F-fluorodeoxyglucose (FDG) uptake in the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas remains unclear. This study aimed to assess the role of FDG uptake in the diagnosis of different degrees of dysplasia of IPMNs. We retrospectively analyzed the following three points in 84 patients with IPMNs: (1) risk factors to predict high-grade dysplasia (HGD) and invasive carcinoma (INV); (2) the relationship between FDG uptake and glucose transporter 1 (GLUT-1) expression; and (3) the relationship between FDG uptake and the presence of mural nodules. The histopathological diagnosis was low-grade dysplasia (LGD) in 43 patients, HGD in 16, and INV in 25. The maximum standardized uptake value (SUV-max) was significantly higher in INV than in LGD/HGD (p < 0.0001, p = 0.0136). The sensitivity and specificity to discriminate INV from LGD/HGD were 80.0% and 86.2%, respectively, using the receiver operator characteristic curve, when the optimal cutoff score of SUV-max was set at 4.03. Those values were not different between HGD and LGD. More than half of HGD patients had low GLUT-1 expression. Taken together, FDG-PET/CT is useful in distinguishing between non-invasive and invasive IPMN. Our results offer critical information that may determine surgical treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Clinical Utility and Limitation of Diagnostic Ability for Different Degrees of Dysplasia of Intraductal Papillary Mucinous Neoplasms of the Pancreas Using 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography

Hozaka

Kurahara

et al. 2021

Cancers

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“…High-level phosphorylation and/or overexpression of RPS6 has been reported in various types of cancers, including acute myeloid leukemia (AML) [ 433 ], breast cancer [ 434 ], cervical cancer [ 435 ], esophageal squamous cell carcinoma (ESCC) [ 436 ], GC [ 437 ], glioblastoma multiforme (GBM) [ 438 ], HNSCC [ 439 ], melanoma [ 440 ], non-Hodgkin’s lymphoma [ 338 ], NSCLC [ 38 ], oral squamous cell carcinoma (OSCC) [ 441 , 442 ], ovarian epithelial cancer (OEC) [ 40 , 443 ], pancreatic cancers [ 13 , 17 , 444 ], renal cell carcinoma (RCC) [ 445 ], sarcoma [ 446 ], and vulva squamous cell carcinoma (VSCC) [ 447 ]. More interestingly, mTOR-independent phosphorylation of RPS6 was frequently identified in primary central nervous system lymphoma (PCNSL) and DLBCL [ 338 , 355 ].…”

Section: Rps6 In Cancermentioning

confidence: 99%

“…Ribosomal protein S6 (RPS6), also known as phosphoprotein NP33 [ 10 ], is a component of the 40S small ribosomal subunit as a ribosomal RNA-binding protein [ 11 , 12 ]. RPS6 is evolutionarily conserved across eukaryotes from yeast to vertebrates [ 12 ] and plays important roles in ribosome biogenesis, protein translation, cell proliferation (increase in cell number), cell growth (increase in cell mass/volume), DNA repair, apoptosis, cell differentiation, and glucose metabolism in both normal and cancer cells [ 13 , 14 , 15 ]. RPS6 is the first ribosomal protein identified to be phosphorylated by protein kinases [ 16 ] and is one of the only two RPs known to be phosphorylated [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?

You

Park

et al. 2021

IJMS

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Ribosomal protein S6 (RPS6) is a component of the 40S small ribosomal subunit and participates in the control of mRNA translation. Additionally, phospho (p)-RPS6 has been recognized as a surrogate marker for the activated PI3K/AKT/mTORC1 pathway, which occurs in many cancer types. However, downstream mechanisms regulated by RPS6 or p-RPS remains elusive, and the therapeutic implication of RPS6 is underappreciated despite an approximately half a century history of research on this protein. In addition, substantial evidence from RPS6 knockdown experiments suggests the potential role of RPS6 in maintaining cancer cell proliferation. This motivates us to investigate the current knowledge of RPS6 functions in cancer. In this review article, we reviewed the current information about the transcriptional regulation, upstream regulators, and extra-ribosomal roles of RPS6, with a focus on its involvement in cancer. We also discussed the therapeutic potential of RPS6 in cancer.

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“…Overexpression of p-S6 is found in various solid tumors, such as gastric cancer, glioblastomas, and renal cell carcinomas (RCCs), and associated with poor prognosis [16][17][18]. S6 phosphorylation was even associated with malignant potential and glucose metabolism of intraductal papillary mucinous neoplasm of the pancreas [19]. In addition, the phosphorylation of S6 is considered to contribute to acquired resistance to MAPK pathway inhibitors in cancers, suggesting that p-S6 plays an essential role in the mechanism of anti-cancer drugs [20,21].…”

Section: Introductionmentioning

confidence: 99%

Overexpressed P-S6 Associates with Lymph Node Metastasis and Predicts Poor Prognosis in Non-Small Cell Lung Cancer.

Tang

Luo

Zhou

et al. 2022

Preprint

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BackgroundRibosomal protein S6 (S6), a downstream effect media of the AKT/mTOR pathway, not only is a part of 40S small subunit of eukaryotic ribosome, but also involves in protein synthesis and cell proliferation during cancer development.MethodsIn present study, we explore the association between phosphorylated S6 (p-S6) protein expression and clinicopathological features as well as prognostic implications in NSCLC. P-S6 was detected in tissue microarrays (TMAs) containing 350 NSCLC, 53 non-cancerous lung tissues (Non-CLT), and 88 cases of matched metastatic lymph node lesions via immunohistochemistry (IHC). Transwell assays and wound healing assay were used to assess the effects of p-S6 inhibition on NSCLC cell metastasis.ResultsThe p-S6 expression in NSCLC was more evident than that in Non-CLT (p < 0.05). Compared to NSCLC patients who have no lymph node metastasis (LNM), those with LNM had higher p-S6 expression (p = 0.001). Regardless of lung squamous cell carcinoma (SCC) or adenocarcinoma (ADC), p-S6 was increased obviously in metastatic lymph nodes compared with matched primary cancers (p = 0.001, p = 0.022, respectively). Inhibition of p-S6 decreased the metastasis ability of NSCLC cells. In addition, p-S6 was an independent predicted marker for LNM in patients with NSCLC (p < 0.001). According to survival analysis, patients with highly expressed p-S6 had a lower survival rate compared with that with lower expression (p = 0.013). P-S6 is an unfavorable independent prognostic factor for NSCLC patients (p = 0.011).Conclusionincreased expression of p-S6 is not only a novel predictive biomarker of LNM but also poor prognosis in NSCLC.

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S6 ribosomal protein phosphorylation is associated with malignancy of intraductal papillary mucinous neoplasm of the pancreas

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 13 publications

References 30 publications

Clinical Utility and Limitation of Diagnostic Ability for Different Degrees of Dysplasia of Intraductal Papillary Mucinous Neoplasms of the Pancreas Using 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography

Clinical Utility and Limitation of Diagnostic Ability for Different Degrees of Dysplasia of Intraductal Papillary Mucinous Neoplasms of the Pancreas Using 18F-Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography

Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?

Overexpressed P-S6 Associates with Lymph Node Metastasis and Predicts Poor Prognosis in Non-Small Cell Lung Cancer.

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