p120-Catenin Downregulation and <i>PIK3CA</i> Mutations Cooperate to Induce Invasion through MMP1 in HNSCC

Kidacki, Michal; Lehman, Heather L.; Green, Michelle V.; Warrick, Joshua I.; Stairs, Douglas B.

doi:10.1158/1541-7786.mcr-17-0108

Cited by 25 publications

(28 citation statements)

References 47 publications

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“…28,29 PIK3CA is the gene coding for the p110α catalytic subunit of PI3K, and PIK3CA mutation can lead to enhanced kinase activity and then continuously stimulate downstream AKT to increase the abilities of tumor cell invasion and metastasis. 30,31 In addition, Figure 10. The effect of silencing or overexpressing hematopoietic-substrate-1 associated protein X-1 (HAX-1) and PIK3CA on SK-Hep1 and SUN387 cells.…”

Section: Discussionmentioning

confidence: 98%

Hematopoietic-substrate-1 associated protein X-1 (HAX-1) regulates liver cancer cells growth, metastasis, and angiogenesis through Akt

et al. 2019

Cancer Biology & Therapy

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The aim of this study was to investigate the effects and mechanisms of hematopoietic-substrate-1-associated protein X-1 (HAX-1) on liver cancer cells. Information on HAX-1 from liver cancer patients was analyzed by the Cancer Genome Atlas (TCGA) program. Cell migration and invasion abilities were respectively tested by scratch assay and transwell assay. Tube formation assay was applied to detect angiogenesis protein and mRNA was determined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. We found that the median month survival of HAX-1 overexpressing liver cancer patients was shorter than that of HAX-1 normal liver cancer patients. HAX-1 was overexpressed in liver cancer tissues and cells, and HAX-1 overexpression promoted the liver cancer cells growth, migration, and invasion, whereas silencing HAX-1 produced the opposite results. Inhibition of Akt by LY294002 reversed the migration and invasion abilities of liver cancer cells, and inhibited the ability of cells growth and angiogenesis. Silencing PIK3CA enhanced the inhibitory effects of HAX-1 silencing on the viability, migration, and invasion of liver cancer cells. HAX-1 affected liver cancer cells metastasis and angiogenesis by affecting Akt phosphorylation and FOXO3A expression.

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Section: Discussionmentioning

confidence: 98%

Hematopoietic-substrate-1 associated protein X-1 (HAX-1) regulates liver cancer cells growth, metastasis, and angiogenesis through Akt

et al. 2019

Cancer Biology & Therapy

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“…Down-regulation or loss of p120ctn has been demonstrated in ESCC as well as eleven other cancer types [ 6 , 37 – 47 ]. Similarly, overexpression of EGFR has been implicated as significant in these cancer types and various others [ 48 – 52 ].…”

Section: Discussionmentioning

confidence: 99%

NFkB hyperactivation causes invasion of esophageal squamous cell carcinoma with EGFR overexpression and p120-catenin down-regulation

et al. 2018

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Four out of five patients diagnosed with esophageal squamous cell carcinoma (ESCC) will die within five years. This is primarily a result of the aggressive invasive potential of the disease. Our research is focused on the interplay between tumor suppressors and oncogenes in the invasive process. Specifically, EGFR and p120-catenin (p120ctn) are commonly dysregulated genes that are indicative of poor prognosis in ESCC. In a previous study we demonstrated that in our 3D organotypic culture model, only when EGFR overexpression is combined with p120ctn inactivation do the cells transform and invade – as opposed to either event alone. The purpose of this present study was to identify the components of the molecular pathways downstream of p120ctn and EGFR that lead to invasion. Using both human esophageal keratinocytes and human ESCC cells, we have identified NFkB as a central regulator of the invasive process downstream of p120ctn down-regulation and EGFR overexpression. Interestingly, we found that NFkB is hyperactivated in cells with EGFR overexpression and p120ctn inactivation than with either EGFR or p120ctn alone. Inhibition of this NFkB hyperactivation results in complete loss of invasion, suggesting that NFkB signaling is necessary for invasion in this aggressive cell type. Furthermore, we have identified RhoA and Rho-kinase as upstream regulators of NFkB in this process. We believe the cooperation of p120ctn down-regulation and EGFR overexpression is not only important in the aggressive mechanisms of ESCC but could be broadly applicable to many other cancer types in which p120ctn and EGFR are involved.

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“…Amongst these genes are those with a previously identified association with tumour progression specifically in HNSCC (Table ). Notably, these include the matrix metalloproteinase MMP1 (Kidacki, Lehman, Green, Warrick, & Stairs, ; Ye et al., ) and the chemokine ligand CCL18 (Jiang et al., ), both molecules implicated in tumour invasion in oral cancer.…”

Section: Discussionmentioning

confidence: 99%

Molecular classification of autofluorescence excision margins in oral potentially malignant disorders

et al. 2018

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p120-Catenin Downregulation and PIK3CA Mutations Cooperate to Induce Invasion through MMP1 in HNSCC

Cited by 25 publications

References 47 publications

Hematopoietic-substrate-1 associated protein X-1 (HAX-1) regulates liver cancer cells growth, metastasis, and angiogenesis through Akt

Hematopoietic-substrate-1 associated protein X-1 (HAX-1) regulates liver cancer cells growth, metastasis, and angiogenesis through Akt

NFkB hyperactivation causes invasion of esophageal squamous cell carcinoma with EGFR overexpression and p120-catenin down-regulation

Molecular classification of autofluorescence excision margins in oral potentially malignant disorders

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