Oncogenic role of LYN in human gastric cancer via the Wnt/β‑catenin and AKT/mTOR pathways

Su, Rui; Zhang, Jun

doi:10.3892/etm.2020.8672

Cited by 8 publications

(13 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lyn is a member of the Src tyrosine kinase family and functions as a proto-oncogene in tumor progression. Lyn is frequently overexpressed in numerous tumor types, including chronic myelogenous leukemia, renal cancer, cervical cancer, head and neck squamous cell carcinoma, gastric cancer, and prostate cancer [ 38 ]. High expression of Mybl2 and Lyn may be associated with the characteristics of iF cells.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression in Pancreatic Cancer-Like Cells and Induced Pancreatic Stem Cells Generated by Transient Overexpression of Reprogramming Factors

Miyagi-Shiohira

Saitoh

Watanabe

et al. 2021

JCM

View full text Add to dashboard Cite

We previously reported that transient overexpression of reprogramming factors can be used to generate induced pluripotent stem (iPS) cells, induced tissue-specific stem (iTS) cells, and fibroblast-like (iF) cells from pancreatic tissue. iF cells have tumorigenic ability and behave similarly to pancreatic cancer cells. In this study, we analyzed gene expression in iF cells and iTS-P cells (iTS cells from pancreatic tissue) via microarray analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression levels of the Mybl2 and Lyn genes, which are reported to be oncogenes, were significantly higher in iF cells than in iTS-P cells. The expression level of Nestin, which is expressed in not only pancreatic progenitor cells but also pancreatic ductal adenocarcinomas, was also higher in iF cells than in iTS-P cells. Itgb6 and Fgf13, which are involved in the pathogenesis of diseases such as cancer, exhibited higher expression levels in iF cells than in iTS-P cells. Unexpectedly, the expression levels of genes related to epithelial-mesenchymal transition (EMT), except Bmp4, were lower in iF cells than in iTS-P cells. These data suggest that the Mybl2, Lyn, Nestin, Itgb6, and Fgf13 genes could be important biomarkers to distinguish iTS-P cells from iF cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Gene Expression in Pancreatic Cancer-Like Cells and Induced Pancreatic Stem Cells Generated by Transient Overexpression of Reprogramming Factors

Miyagi-Shiohira

Saitoh

Watanabe

et al. 2021

JCM

View full text Add to dashboard Cite

show abstract

“…LYN activation sensitizes insulin receptors [ 132 , 133 ], and increases glucose transport [ 128 , 134 ]. LYN is an important player in multiple tumor-related functions [ 135 ] and is upregulated in cervical cancers [ 136 ], prostate cancers [ 137 ], colon cancer [ 135 ], and Ewing’s sarcoma [ 138 ]. Further, LYN expression predicts poor prognoses for renal cancer patients [ 139 ], head and neck squamous cell carcinoma patients [ 140 ], nonsmall cell lung cancer patients [ 141 ], and breast cancer patients [ 142 ].…”

Section: Lck/yes-related Novel Kinase (Lyn)mentioning

confidence: 99%

“…ABL2 inhibition decreases CXCL12/CXCR4-induced cancer cell invasion [ 91 ]. LYN inhibition increases cancer cell apoptosis, and reduces cancer cell proliferation, migration, and invasion, likely by inactivating the WNT/Beta-Catenin and AKT/mTOR pathways and activating the mitochondrial apoptotic pathway [ 135 ]. FYN inhibition decreases migration and invasion, possibly via STAT3 signaling [ 255 ].…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

“…LYN activation sensitizes insulin receptors [132,133], and increases glucose transport [128,134]. LYN is an important player in multiple tumor-related functions [135] and is upregulated in cervical cancers An insightful review by Moll and colleagues documents additional points that highlight the atypical landscape of current DDR1 research [116]. In brief, these include a paucity of laboratories investigating DDR1 in inflammatory cells; a string of retractions undermining aspects of the topic's knowledge base; absence of a commercially available DDR1-specific human antibody; and-in at least one study-a striking contrast between in vitro and in vivo results.…”

Section: Lck/yes-related Novel Kinase (Lyn)mentioning

confidence: 99%

See 1 more Smart Citation

Emerging Kinase Therapeutic Targets in Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer Desmoplasia

Creeden

Alganem

Imami

et al. 2020

IJMS

View full text Add to dashboard Cite

Kinase drug discovery represents an active area of therapeutic research, with previous pharmaceutical success improving patient outcomes across a wide variety of human diseases. In pancreatic ductal adenocarcinoma (PDAC), innovative pharmaceutical strategies such as kinase targeting have been unable to appreciably increase patient survival. This may be due, in part, to unchecked desmoplastic reactions to pancreatic tumors. Desmoplastic stroma enhances tumor development and progression while simultaneously restricting drug delivery to the tumor cells it protects. Emerging evidence indicates that many of the pathologic fibrotic processes directly or indirectly supporting desmoplasia may be driven by targetable protein tyrosine kinases such as Fyn-related kinase (FRK); B lymphoid kinase (BLK); hemopoietic cell kinase (HCK); ABL proto-oncogene 2 kinase (ABL2); discoidin domain receptor 1 kinase (DDR1); Lck/Yes-related novel kinase (LYN); ephrin receptor A8 kinase (EPHA8); FYN proto-oncogene kinase (FYN); lymphocyte cell-specific kinase (LCK); tec protein kinase (TEC). Herein, we review literature related to these kinases and posit signaling networks, mechanisms, and biochemical relationships by which this group may contribute to PDAC tumor growth and desmoplasia.

show abstract

“…Schwarz et al showed that LYNactivating mutations were associated with antiestrogen resistance for breast cancer patients with estrogen receptorpositive (37). LYN also acted as the tumor driver in gastric cancer cells via activation of the mitochondrial apoptotic pathway and inhibition of the Wnt/β-catenin and AKT/mTOR pathways (38). LCK was detectable in multiple cancer types, including breast cancer (39), colon cancer (40), and lung carcinoma (41).…”

mentioning

confidence: 99%

Comprehensively investigating the expression levels and the prognostic role of transforming growth factor beta-induced (TGFBI) in glioblastoma multiforme

Yin¹,

Liu²,

Feng³

et al. 2020

Transl Cancer Res TCR

View full text Add to dashboard Cite

Background: Transforming growth factor beta-induced (TGFBI) protein has been found expressed in several cancer types, and expression levels of TGFBI can affect the cancer patients' outcomes, but the role of TGFBI in glioblastoma multiforme (GBM) remains obscure. Methods:The TGFBI expression levels in GBM were performed via Gene Expression Profiling Interactive Analysis (GEPIA) and UALCAN databases. Further, the mutations types of TGFBI were analyzed by using the cBioportal dataset. LinkedOmics selected correlated genes, kinases, and microRNA (miRNA) targets of TGFBI. GEPIA conducted the prognostic value of TGFBI and correlated genes. Then, the relationship between TGFBI and immune infiltrates was performed by Tumor Immune Estimation Resource (Timer).We compared the TGFBI protein expression levels in GBM and control samples through the Human Protein Atlas (HPA). Finally, the GSCAlite was used to achieve the drugs, and molecules target the TGFBI and significantly correlated genes.Results: TGFBI is significantly overexpressed in GBM, but the clinical features do not have considerable influence on TGFBI expression levels. Overexpression of TGFBI acts as an adverse biomarker of GBM.The enrichment function of TGFBI showed that the main biological functions, including extracellular matrix (ECM) organization, angiogenesis, leukocyte migration, T cell activation, cell cycle G2/M phase transition, and growth factor binding. About the significant correlated genes, overexpression of mitogenactivated protein kinase 13 (MAPK13) [Log-rank P=0.08 HR (high) =1.4], myosin IG (MYO1G) [Log-rank P=0.06 HR (high) =1.4], plasminogen activator urokinase receptor (PLAUR) [Log-rank P=0.03 HR (high) =1.5], thrombomodulin (THBD) [Log-rank P=0.028 HR (high) =1.5] indicated the poor prognosis of GBM.Further, TGFBI had a significant association with dendritic cell (DC) infiltrates (cor =0.516, P=9.00e−30).The higher the DC infiltration, the shorter survival of GBM. TGFBI protein expression levels were not significantly different in GBM and normal tissue. Finally, TGFBI is associated with resistance to belinostat, LAQ824, CAY10603, CUDC-101, methotrexate, 5-fluorouracil, and navitoclax. Conclusions:In the present study, we showed TGFBI was overexpressed in GBM, and TGFBI is associated with DC cell infiltrates. Overexpression of TGFBI and high DC infiltration might be an adverse biomarker of GBM. Finally, TGFBI is associated with tumor multi-drug resistance.

show abstract

Oncogenic role of LYN in human gastric cancer via the Wnt/β‑catenin and AKT/mTOR pathways

Cited by 8 publications

References 41 publications

Gene Expression in Pancreatic Cancer-Like Cells and Induced Pancreatic Stem Cells Generated by Transient Overexpression of Reprogramming Factors

Gene Expression in Pancreatic Cancer-Like Cells and Induced Pancreatic Stem Cells Generated by Transient Overexpression of Reprogramming Factors

Emerging Kinase Therapeutic Targets in Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer Desmoplasia

Comprehensively investigating the expression levels and the prognostic role of transforming growth factor beta-induced (TGFBI) in glioblastoma multiforme

Contact Info

Product

Resources

About