Krüppel-like factor 8 involved in hypoxia promotes the invasion and metastasis of gastric cancer via epithelial to mesenchymal transition

Liu, Na; Wang, Yafang; Zhou, Yunyun; Pang, Hailin; Zhou, Jing; Pei, Qian; Liu, Huan; Zhang, Helong

doi:10.3892/or.2014.3495

Cited by 26 publications

(27 citation statements)

References 42 publications

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“…In agreement with our finding, a number of previous studies have demonstrated that ectopic expression of KLF8 repressed E-cadherin expression, induced tumor cell EMT, and increased cell invasion and metastasis in breast cancer (6,22) and hepatocellular carcinoma (17). Furthermore, downregulation of KLF8 may inhibit cell invasion and metastasis in gastric cancer (23,24).…”

Section: Discussionsupporting

confidence: 81%

“…An increasing number of transcription factors have been implicated in the repression of E-cadherin expression, including KLF transcription factor family proteins (6,23). KLF8 is a relatively new member of this family and is emerging as a crucial regulator of cancer initiation and progression (10).…”

Section: Discussionmentioning

confidence: 99%

“…As a GT-box (CACCC) binding dual-transcription factor, KLF8 regulates the transcription of numerous genes by recruiting the C-terminal binding protein (CtBP) corepressor (6-10) or p300 and P300/CtBP-associated factor histone acetyltransferase co-activators (8,(11)(12)(13)(14) in order to target gene promoters. It is aberrantly overexpressed in a number of cancer subtypes and has been implicated in the initiation, development and progression of these cancer subtypes, including hepatocellular carcinoma (15)(16)(17), gastric cancer (18)(19)(20)(21), breast cancer (22,23), ovarian cancer (14,24), renal cancer (22,25) and glioma (26). It is worth noting that KLF8 induced tumor cell epithelial-to-mesenchymal transition (EMT) and maintained the invasive potential of cancer, which appeared to serve a critical role in the metastatic progression of cancer cells (6,27).…”

Section: Introductionmentioning

confidence: 99%

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Krüppel-like factor 8 induces epithelial-to-mesenchymal transition and promotes invasion of pancreatic cancer cells through transcriptional activation of four and a half LIM-only protein 2

Zai

Long

et al. 2017

Oncology Letters

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Abstract. Pancreatic cancer (PC) is one of the most aggressive types of cancer with an extremely poor prognosis. Invasive growth and early metastasis is one of the greatest challenges to overcome for the treatment of PC. Numerous previous studies have indicated that the transcription factor Krüppel-like factor 8 (KLF8) and nuclear cofactor four and a half LIM-only protein 2 (FHL2) serve important roles in tumorigenesis and tumor progression; however, their roles in PC remain elusive. The present study revealed that KLF8 and FHL2 expression is aberrantly co-overexpressed in PC tissue samples and associa ted with tumor metastasis. Furthermore, a positive correlation between the expression levels of KLF8 and FHL2 was observed. Subsequently, the present study identified KLF8 as a critical inducer of epithelial-to-mesenchymal transition (EMT) and invasion. Of note, the present study demonstrated that KLF8 overexpression induced a strong increase in FHL2 expression, and subsequent promoter reporter assays determined that KLF8 directly bound and activated the FHL2 gene promoter. Furthermore, FHL2 knockdown in KLF8-overexpressing cells partially reversed the EMT and invasive phenotypes. The present study identified KLF8-induced FHL2 activation as a novel and critical signaling mechanism underlying human PC invasion.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Krüppel-like factor 8 induces epithelial-to-mesenchymal transition and promotes invasion of pancreatic cancer cells through transcriptional activation of four and a half LIM-only protein 2

Zai

Long

et al. 2017

Oncology Letters

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“…KLF17 enhances Twist expression and consequently triggers EMT in endometrial cancer 27. KLF8 promotes the migration and invasion of gastric cancer cells by triggering EMT under hypoxic conditions 28. In our study, KLF6 inhibited the expression of mesenchymal markers, such as snail, slug, and vimentin.…”

Section: Discussionsupporting

confidence: 49%

KLF6 inhibited oral cancer migration and invasion via downregulation of mesenchymal markers and inhibition of MMP-9 activities

Hsu¹,

Huang²,

Lai³

et al. 2017

Int. J. Med. Sci.

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Krüppel-like factors can bind to specific DNA motifs and regulate various cellular functions, such as metabolism, cell proliferation, and differentiation. Krüppel-like factor 6 (KLF6), a member of this family, is downregulated in human cancers. Oral cancer is a highly prevalent type in Taiwan. Although KLF6 overexpression in human cancer cells inhibits cell proliferation, induces apoptosis, and attenuates cell migration, the effects of KLF6 on oral cancer remains poorly elucidated. This study investigated the role of KLF6 in oral cancer tumorigenesis. Immunohistochemical staining revealed that nuclear KLF6 level was significantly and inversely associated with tumor size and stages. KLF6 overexpression attenuated the migration and invasion of oral cancer SAS cells. Zymography assay demonstrated that KLF6 inhibited the activities of matrix metalloproteinase 9 (MMP-9) and weakened the expression of mesenchymal markers, such as snail, slug, and vimentin. Our study is the first to provide demonstrate that KLF6 functions as a tumor suppressor gene and prevents the metastasis of oral cancer cells.

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“…2), a dual transcription factor implicated in cancer of many types 29,[32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] that promotes the expression of EPSTI1 by transcriptional activation of the gene promoter. 23 Notably, KLF8 has been demonstrated to potently induce EMT by repressing E-cadherin 45 and cancer stem cell traits.…”

Section: Introductionmentioning

confidence: 99%

Implications of Epithelial–Stromal Interaction 1 in Diseases Associated with Inflammatory Signaling

Gray

Zhao

2016

Cell Communication Insights

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Epithelial-stromal interaction 1 (EPSTI1) was initially identified as an induced gene in breast cancer epithelial cells by cocultured stromal fibroblasts. This discovery led to further investigation and understanding of the role of EPSTI1 in cancer. Aberrant elevation of EPSTI1 occurs primarily in invasive breast cancer epithelial cells. Forced overexpression of EPSTI1 in noninvasive cancer cells can substitute for the stromal fibroblasts. EPSTI1 was further implicated in cancer by our most recent study that identified it as one of the few most upregulated genes in human breast cancer by Krüppel-like factor 8 (KLF8), a pro-cancerous transcription factor in many cancer types. Our study also demonstrated that EPSTI1 interacts with valosin-containing protein to promote the degradation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) inhibitor alpha, leading to the activation and nuclear translocation of NF-κB. Additionally, EPSTI1 was shown to inhibit apoptosis by inactivating caspase 8. Studies on hepatitis C and E viruses have indicated that EPSTI1 plays a role in inhibition of the viral replication by promoting the expression of protein kinase R or protein kinase RNA-activated, a viral response gene, suggesting a role of EPSTI1 in immune response. Interestingly, in addition to transducing stromal signals, EPSTI1 has been implicated in immune privilege and autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and histiocytic necrotizing lymphadenitis. This review seeks to comb EPSTI1-related studies as it was cloned a dozen years ago with a particular focus on the mechanisms of its regulation and signaling, as well as its potential roles in the diseases.

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Krüppel-like factor 8 involved in hypoxia promotes the invasion and metastasis of gastric cancer via epithelial to mesenchymal transition

Cited by 26 publications

References 42 publications

Krüppel-like factor 8 induces epithelial-to-mesenchymal transition and promotes invasion of pancreatic cancer cells through transcriptional activation of four and a half LIM-only protein 2

Krüppel-like factor 8 induces epithelial-to-mesenchymal transition and promotes invasion of pancreatic cancer cells through transcriptional activation of four and a half LIM-only protein 2

KLF6 inhibited oral cancer migration and invasion via downregulation of mesenchymal markers and inhibition of MMP-9 activities

Implications of Epithelial–Stromal Interaction 1 in Diseases Associated with Inflammatory Signaling

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Krüppel-like factor 8 involved in hypoxia promotes the invasion and metastasis of gastric cancer via epithelial to mesenchymal transition

Cited by 26 publications

References 42 publications

Krüppel-like factor 8 induces epithelial-to-mesenchymal transition and promotes invasion of pancreatic cancer cells through transcriptional activation of four and a half LIM-only protein 2

Krüppel-like factor 8 induces epithelial-to-mesenchymal transition and promotes invasion of pancreatic cancer cells through transcriptional activation of four and a half LIM-only protein 2

KLF6 inhibited oral cancer migration and invasion via downregulation of mesenchymal markers and inhibition of MMP-9 activities

Implications of Epithelial&ndash;Stromal Interaction 1 in Diseases Associated with Inflammatory Signaling

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Implications of Epithelial–Stromal Interaction 1 in Diseases Associated with Inflammatory Signaling