Stratifin accelerates progression of lung adenocarcinoma at an early stage

Shiba-Ishii, Aya; Kim, Yunjung; Shiozawa, Toshihiro; Iyama, Shinji; Satomi, Kaishi; Kano, Junko; Sakashita, Shingo; Morishita, Yukio; Noguchi, Masayuki

doi:10.1186/s12943-015-0414-1

Cited by 43 publications

(51 citation statements)

References 17 publications

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“…We had previously found that depletion of SFN decreased cell growth in vitro and tumor progression or development in vivo, suggesting that SFN might be a promising therapeutic target for lung adenocarcinoma (12). Here, we revealed that SFN enhances tumor progression through binding with SKP1 and blocking of oncoprotein ubiquitination.…”

Section: Interaction Of Sfn With Skp1 Is Competitive With Fbw7mentioning

confidence: 59%

“…Moreover, its overexpression is significantly associated with poorer prognosis in patients with breast cancer (8), hepatocellular carcinoma (9), colorectal carcinoma (10), and endometrial carcinoma (11). Our in vitro and in vivo functional analysis has also indicated that SFN regulates cell-cycle progression in a positive manner and promotes the progression of lung adenocarcinoma (12). Importantly, 30% of SFN-transgenic mice with lung-specific expression of human SFN spontaneously developed lung tumors, suggesting that SFN is a potent oncogene.…”

Section: Introductionmentioning

confidence: 61%

“…Moreover, because SFN is known to be an anchor protein that binds to various intercellular molecules, we previously screened SFN-specific binding partner(s) in lung adenocarcinoma cells using pulldown assay and LC-MS/MS analysis in order to clarify the molecular mechanism by which SFN facilitates tumor progression (13). Among the listed proteins, in the present study we focused on S-phase kinase-associated protein 1 (SKP1), which is an adaptor part of the SCF E3 ubiquitin ligase complex, as our previous results had shown that suppression of SFN reduced the S-phase subpopulation, implying an association of SFN with S-phase of the cell cycle (12). SCF ubiquitin ligases constitute a subset of the cullin ring ligase family and are the largest family of E3 ubiquitin ligases in mammals.…”

Section: Introductionmentioning

confidence: 99%

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Stratifin Inhibits SCFFBW7 Formation and Blocks Ubiquitination of Oncoproteins during the Course of Lung Adenocarcinogenesis

Shiba-Ishii

Hong

Hirokawa

et al. 2019

Clinical Cancer Research

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Purpose: Aberrant overexpression of SFN (stratifin) plays an oncogenic role in lung adenocarcinoma. We have shown previously that SKP1, an adapter component of E3 ubiquitin ligase forming an SCF complex, is a unique SFN-binding protein in lung adenocarcinoma cells.Experimental Design: In silico simulation and in vitro mutagenesis analysis were performed to identify the SFN-binding domain on SKP1. We examined expression, localization, and stability of SKP1 after knockdown of SFN using lung adenocarcinoma cells including A549. In silico library screening and experimental validation were used for drug screening. Daily oral administration of each candidate drugs to A549-injected tumor-bearing mice was performed to evaluate their in vivo antitumor efficacy.Results: Suppression of SFN upregulated the stability of SKP1 and accelerated its cytoplasm-to-nucleus translocation. Consistently, IHC analysis revealed that cytoplasmic expres-sion of SKP1 was significantly associated with SFN positivity, tumor malignancy, and poorer patient outcome. After SFN suppression, ubiquitination of oncoproteins, including p-cyclin E1, p-c-Myc, p-c-Jun, and cleaved Notch 1, which are target proteins of SCF FBW7 , was strongly induced. These results indicate that SFN-SKP1 binding results in SCF FBW7 dysfunction and allows several oncoproteins to evade ubiquitination and subsequent degradation. Because inhibition of SFN-SKP1 binding was expected to have antitumor efficacy, we next searched for candidate SFN inhibitors. Aprepitant and ticagrelor were finally selected as potential SFN inhibitors that dose dependently reduced SFN-SKP1 binding and tumor progression in vivo.Conclusions: As overexpression of SFN is detectable in most adenocarcinoma, we believe that SFN inhibitors would be novel and promising antitumor drugs for lung adenocarcinoma.

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Section: Interaction Of Sfn With Skp1 Is Competitive With Fbw7mentioning

confidence: 59%

Section: Introductionmentioning

confidence: 61%

Section: Introductionmentioning

confidence: 99%

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Stratifin Inhibits SCFFBW7 Formation and Blocks Ubiquitination of Oncoproteins during the Course of Lung Adenocarcinogenesis

Shiba-Ishii

Hong

Hirokawa

et al. 2019

Clinical Cancer Research

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“…Non-gastric cancer SFN speed up lung adenocarcinoma development in an early stage (Shiba-Ishii et al, 2015).…”

Section: -3-3 Protein Sigma (Sfn)mentioning

confidence: 99%

Helicobacter pyloriouter inflammatory protein A (OipA) suppresses apoptosis of AGS gastric cells in vitro

Al-Maleki

Loke

Lui

et al. 2017

Cellular Microbiology

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Outer inflammatory protein A (OipA) is an important virulence factor associated with gastric cancer and ulcer development; however, the results have not been well established and turned out to be controversial. This study aims to elucidate the role of OipA in Helicobacter pylori infection using clinical strains harbouring oipA "on" and "off" motifs. Proteomics analysis was performed on AGS cell pre-infection and postinfection with H. pylori oipA "on" and "off" strains, using liquid chromatography/mass spectrometry. AGS apoptosis and cell cycle assays were performed. Moreover, expression of vacuolating cytotoxin A (VacA) was screened using Western blotting. AGS proteins that have been suggested previously to play a role or associated with gastric disease were down-regulated postinfection with oipA "off" strains comparing to oipA "on" strains. Furthermore, oipA "off" and ΔoipA cause higher level of AGS cells apoptosis and G0/G1 cell-cycle arrest than oipA "on" strains. Interestingly, deletion of oipA increased bacterial VacA production. The capability of H. pylori to induce apoptosis and suppress expression of proteins having roles in human disease in the absence of oipA suggests that strains not expressing OipA may be less virulent or may even be protective against carcinogenesis compared those expressing OipA. This potentially explains the higher incidence of gastric cancer in East Asia where oipA "on" strains predominates.

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“…11 Elevated expression of 14-3-3σ has been shown to arrest the cell cycle at the G2 phase of colon and breast cancer cells. 12,13 By contrast, in an oncogenic role, ectopic expression of 14-3-3σ has been reported to promote proliferation of lung cancer cells, 14 and motility or invasion of colon 15 and breast 16 cancer cells. These different roles have also been demonstrated in a clinical setting.…”

Section: Introductionmentioning

confidence: 98%

Down-Regulation of 14-3-3σ Reduces Proliferation of Human Lung Cancers But Not Colon Cancer Cells

Nunun¹,

Thongsuksai

Trakunrum

et al. 2018

J Health Sci Med Res

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Abstract:Objective: 14-3-3σ protein is well known for its tumor suppressive function in breast cancer. However, recent evidence has raised the possibility that the 14-3-3σ protein may also have an oncogenic function in certain cancer types. The aim of this study was to investigate the oncogenic function of 14-3-3σ in adenocarcinoma cell lines of the lung (A549, H358) and colon (HT-29). Material and Methods: siRNA against 14-3-3σ was used to suppress 14-3-3σ expression. Cell proliferation, cell-cycle distribution and expression of related molecules were determined by MTT, flow cytometry, and western blotting, respectively. Results: Down-regulation of 14-3-3σ significantly reduced the proliferation of A549 and H358 by 35.0% and 31.0%, respectively, and significantly induced cell cycle arrest at the G0/G1 and G2/M phases, respectively. Increased p21 expression by 43.0% was only observed in si-14-3-3σ-H358 cells. The si-14-3-3σ-HT-29 cells showed no alteration of cell proliferation and cell-cycle distribution but harbored reduced p53 expression by 56.0% and p27 expression by 67.0%. Conclusion: 14-3-3σ may have an oncogenic function in lung adenocarcinoma but play a different role in colon cancer.Keywords: 14-3-3σ, cancer, cell proliferation, siRNA

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Stratifin accelerates progression of lung adenocarcinoma at an early stage

Cited by 43 publications

References 17 publications

Stratifin Inhibits SCFFBW7 Formation and Blocks Ubiquitination of Oncoproteins during the Course of Lung Adenocarcinogenesis

Stratifin Inhibits SCFFBW7 Formation and Blocks Ubiquitination of Oncoproteins during the Course of Lung Adenocarcinogenesis

Helicobacter pyloriouter inflammatory protein A (OipA) suppresses apoptosis of AGS gastric cells in vitro

Down-Regulation of 14-3-3σ Reduces Proliferation of Human Lung Cancers But Not Colon Cancer Cells

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