Enigma Plays Roles in Survival of Thyroid Carcinoma Cells through PI3K/AKT Signaling and Survivin

Kim, Yoonjung; Hwang, Hyo-Jeong; Kang, Jun Goo; Kim, Chul Sik; Ihm, Sung-Hee; Choi, Moon Gi; Lee, Seong Jin

doi:10.21873/anticanres.12623

Cited by 10 publications

(11 citation statements)

References 29 publications

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“…Silencing of Survivin in HeLa cells (cervical carcinoma cells) was shown to result in an increased sensitivity to radiation therapy [ 70 ]. Several studies on thyroid carcinoma (THYR) cell lines demonstrate the involvement of Survivin in inhibiting cell proliferation [ 71 – 73 ] and an in vivo study using human gastric adenocarcinoma cell lines in mice xenografts showed that inhibition of Survivin expression could promote cell death [ 74 ].…”

Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis identifies BIRC5 as a prognostic biomarker

et al. 2022

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Background The BIRC5 gene encodes for the Survivin protein, which is a member of the inhibitor of apoptosis family. Survivin is found in humans during fetal development, but generally not in adult cells thereafter. Previous studies have shown that Survivin is abundant in most cancer cells, thereby making it a promising target for anti-cancer drugs and a potential prognostic tool. Methods To assess genetic alterations and mutations in the BIRC5 gene as well as BIRC5 co-expression with other genes, genomic and transcriptomic data were downloaded via cBioPortal for approximately 9000 samples from The Cancer Genome Atlas (TCGA) representing 33 different cancer types and 11 pan-cancer organ systems, and validated using the ICGC Data Portal and COSMIC. TCGA BIRC5 RNA sequencing data from 33 different cancer types and matching normal tissue samples for 16 cancer types were downloaded from Broad GDAC Firehose and validated using breast cancer microarray data from our previous work and data sets from the GENT2 web-based tool. Survival data were analyzed with multivariable Cox proportional hazards regression analysis and validated using KM plotter for breast-, ovarian-, lung- and gastric cancer. Results Although genetic alterations in BIRC5 were not common in cancer, BIRC5 expression was significantly higher in cancer tissue compared to normal tissue in the 16 different cancer types. For 14/33 cancer types, higher BIRC5 expression was linked to worse overall survival (OS, 4/14 after adjusting for both age and tumor grade and 10/14 after adjusting only for age). Interestingly, higher BIRC5 expression was associated with better OS in lung squamous cell carcinoma and ovarian serous cystadenocarcinoma. Higher BIRC5 expression was also linked to shorter progressive-free interval (PFI) for 14/33 cancer types (4/14 after adjusting for both age and tumor grade and 10/14 after adjusting only for age). External validation showed that high BIRC5 expression was significantly associated with worse OS for breast-, lung-, and gastric cancer. Conclusions Our findings suggest that BIRC5 overexpression is associated with the initiation and progression of several cancer types, and thereby a promising prognostic biomarker.

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Section: Discussionmentioning

confidence: 99%

Pan-cancer analysis identifies BIRC5 as a prognostic biomarker

et al. 2022

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“…PI3K/AKT signaling orchestrates many intracellular processes essential for survival of healthy cells (29). In thyroid carcinoma cells, it has been shown that aberrant activation of PI3K/AKT signaling participates in neoplastic transformation, and PI3K/AKT signaling plays pivotal roles in cell survival in our previous reports (30)(31)(32)(33)(34)(35)(36)(37). With respect to the involvement of PI3K/AKT signaling in evodiamineinduced antitumor action, it has been shown that evodiamine enhances the therapeutic efficacy of gemcitabine via direct or indirect negative regulation of PI3K/AKT signaling in in vitro and in vivo models of pancreatic cancer (12).…”

Section: Discussionmentioning

confidence: 95%

“…The p21, p53 and matrix metalloproteinases are related to proliferation, migration, invasion and metastasis of cancer cells (41)(42)(43). In this regard, we have previously reported that p21, p53, MMP-2 and MMP-9 are responsible for proliferation and migration of thyroid carcinoma cells (37,44). Besides its cytostatic and cytotoxic effects, evodiamine impedes cancer progression through interruption of migration, invasion and metastasis of cancer cells (5,16).…”

Section: Discussionmentioning

confidence: 97%

Evodiamine Suppresses Survival, Proliferation, Migration and Epithelial–Mesenchymal Transition of Thyroid Carcinoma Cells

et al. 2018

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Background/Aim: The aim of this study was to evaluate the effect of evodiamine alone or in combination with chemotherapeutic agents on thyroid carcinoma cells. Materials and Methods: TPC-1 and SW1736 thyroid carcinoma cells were used. Cell viability, cytotoxic activity, apoptosis and migration were examined by applying appropriate methods. Drug combination analysis was performed. Results: Evodiamine treatment of cells decreased cell viability, and Bcl2 and phospho-AKT protein levels. Cytotoxic activity and the percentage of apoptotic cells increased. After co-treatment of wortmannin, cell viability, and phospho-AKT and Bcl2 protein levels decreased, and cytotoxic activity increased. In transforming growth factor-β-treated cells, evodiamine attenuated variations in morphology, growth and migration, and increased p21 and p53 protein levels, and decreased β-catenin, N-cadherin, vimentin, phospho-AKT, matrix metalloproteinase-2 and matrix metalloproteinase-9 protein levels. When cells were treated with both evodiamine and chemotherapeutic agents, all combination index values were lower than 1.0. Conclusion: Evodiamine was cytotoxic towards thyroid carcinoma cells, and repression of AKT reinforced evodiamineinduced cytotoxicity. Furthermore, evodiamine ameliorated proliferation, migration and epithelial-mesenchymal transition, and synergized with chemotherapeutic agents.

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“…We performed network analysis using IPA on the list of differentially expressed proteins in both the diffuse and intestinal subtypes of gastric cancer. IPA network analysis of the diffuse subtype showed upregulation of proteins like HSPB1 [ 37 , 38 ], KCTD [ 39 , 40 , 41 , 42 ], TPM3 [ 43 , 44 , 45 , 46 ], PDLIM7 [ 47 , 48 , 49 ], LUZP1 [ 50 ], ACTN1 [ 51 , 52 ], and CFL2 [ 53 ], which have oncogenic properties in the topmost network ( Supplementary Figure S1 ). These proteins are involved in promoting tumor growth, invasion and resistance to anti-tumor therapy in various cancers including gastric cancer.…”

Section: Resultsmentioning

confidence: 99%

Proteomic Signatures of Diffuse and Intestinal Subtypes of Gastric Cancer

Singh

Bhat

Sathe

et al. 2021

Cancers

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Gastric cancer is a leading cause of death from cancer globally. Gastric cancer is classified into intestinal, diffuse and indeterminate subtypes based on histology according to the Laurén classification. The intestinal and diffuse subtypes, although different in histology, demographics and outcomes, are still treated in the same fashion. This study was designed to discover proteomic signatures of diffuse and intestinal subtypes. Mass spectrometry-based proteomics using tandem mass tags (TMT)-based multiplexed analysis was used to identify proteins in tumor tissues from patients with diffuse or intestinal gastric cancer with adjacent normal tissue control. A total of 7448 or 4846 proteins were identified from intestinal or diffuse subtype, respectively. This quantitative mass spectrometric analysis defined a proteomic signature of differential expression across the two subtypes, which included gremlin1 (GREM1), bcl-2-associated athanogene 2 (BAG2), olfactomedin 4 (OLFM4), thyroid hormone receptor interacting protein 6 (TRIP6) and melanoma-associated antigen 9 (MAGE-A9) proteins. Although GREM1, BAG2, OLFM4, TRIP6 and MAGE-A9 have all been previously implicated in tumor progression and metastasis, they have not been linked to intestinal or diffuse subtypes of gastric cancer. Using immunohistochemical labelling of a tissue microarray comprising of 124 cases of gastric cancer, we validated the proteomic signature obtained by mass spectrometry in the discovery cohort. Our findings should help investigate the pathogenesis of these gastric cancer subtypes and potentially lead to strategies for early diagnosis and treatment.

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Enigma Plays Roles in Survival of Thyroid Carcinoma Cells through PI3K/AKT Signaling and Survivin

Abstract: Enigma affects cell survival through modulation of phosphatidylinositol-3 kinase/AKT signaling and survivin, and regulates cell proliferation and migration via involvement of MMP-2, MMP-9, p53 and p21 in thyroid carcinoma cells.

Cited by 10 publications

References 29 publications

Pan-cancer analysis identifies BIRC5 as a prognostic biomarker

Pan-cancer analysis identifies BIRC5 as a prognostic biomarker

Evodiamine Suppresses Survival, Proliferation, Migration and Epithelial–Mesenchymal Transition of Thyroid Carcinoma Cells

Proteomic Signatures of Diffuse and Intestinal Subtypes of Gastric Cancer

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