Up-regulation of Krüppel-Like Factor 8 Promotes Tumor Invasion and Indicates Poor Prognosis for Hepatocellular Carcinoma

Li, Jiachu; Yang, Xin‐Rong; Sun, Haixiang; Xu, Yang; Zhou, Jian; Qiu, Shuang–Jian; Ke, Ai–Wu; Cui, Yuehong; Wang, Zhi–Jun; Wang, Weimin; Liu, Kang–Da; Fan, Jia

doi:10.1053/j.gastro.2010.08.004

Cited by 85 publications

(87 citation statements)

References 38 publications

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“…Based on the exogenous overexpression experiments in vitro, KLF8 was revealed to be a potent inducer of EMT. 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%

“…pcDNA3.1 vectors expressing KLF8 or mock messenger RNA (mRNA) were constructed, as previously described (17). KLF8 or mock vectors were transfected into Panc-1 cells using Lipofectamine 2000 reagent (Invitrogen; Thermo Fisher Scientific, Inc.).…”

Section: Western Blotting (Wb)mentioning

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: Western Blotting (Wb)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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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“…A study by Fu et al (12) demonstrated that the expression of KLF8 protein and mRNA is higher in tumorous tissue compared with normal tissue. Another study (13) revealed that the expression of KLF8 was higher in hepatocellular carcinoma with high metastatic ability. The aforementioned observations indicate that KLF8 promotes tumor development and is important in the processes of invasion and metastasis.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have reported KLF8 overexpression in breast cancer, hepatocellular carcinoma and renal cancer (11)(12)(13); therefore, KLF8 may function as a predictor of metastasis and overall survival in certain types of cancer. However, the expression of KLF8 in NPC cell lines and its effects on NPC cells have not yet been investigated.…”

Section: Introductionmentioning

confidence: 99%

Small hairpin RNA-mediated Krüppel-like factor 8 gene knockdown inhibits invasion of nasopharyngeal carcinoma

Wang

Cao

et al. 2015

Oncology Letters

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Abstract. The present study aimed to characterize the expression of Krüppel-like factor 8 (KLF8) in nasopahryngeal carcinoma (NPC) cell lines and determine its effect on tumor development and invasion following KLF8 gene knockdown by small hairpin RNA (shRNA). KLF8 expression in four NPC cell lines was examined by quantitative polymerase chain reaction (qPCR) and western blotting. KLF8 was knocked down in the SUNE1-5-8F/Sh-KLF8 cell line using shRNA, and the resulting stable cell line SUNE1-5-8F-sh-KLF8 was transplanted into nude mice in order to observe tumor formation and invasion. The results obtained from qPCR and western blotting revealed that, of the four NPC cell lines, KLF8 expression was lowest in the CNE-1 cells and highest in the SUNE1-5-8F cells. The tumor xenograft mouse models revealed that SUNE1-5-8F/Sh-KLF8 cells had a reduced ability for tumor formation and invasion compared with the control group. These results demonstrated for the first time that KLF8 modulates the formation and invasive ability of nasopharyngeal carcinoma.

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PELI1 promotes radiotherapy sensitivity by inhibiting noncanonical NF‐κB in esophageal squamous cancer

et al. 2021

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The low sensitivity of radiotherapy is the main cause of tumor tolerance against ionizing radiation (IR). However, the molecular mechanisms by which radiosensitivity is controlled remain elusive. Here, we observed that high expression of pellino E3 ubiquitin protein ligase 1 (PELI1) was correlated with improved prognosis in human esophageal squamous cell carcinoma stage III patients that received adjuvant radiotherapy. Moreover, we found PELI1-mediated IR-induced tumor cell apoptosis in vivo and in vitro. Mechanistically, PELI1 mediated the lysine 48 (Lys48)-linked polyubiquitination and degradation of NF-κB-inducing kinase (NIK; also known as MAP3K14), the master kinase of the noncanonical NF-κB pathway, thereby inhibiting IR-induced activation of the noncanonical NF-κB signaling pathway during radiotherapy. As a consequence, PELI1 inhibited the noncanonical NF-κB-induced expression of the anti-apoptotic gene BCL2 like 1 (Bclxl; also known as BCL2L1), leading to an enhancement of the IR-induced apoptosis signaling pathway and ultimately promoting IRinduced apoptosis in tumor cells. Therefore, Bclxl or NIK knockdown abolished the apoptosis-resistant effect in PELI1-knockdown tumor cells after radiotherapy. These findings establish PELI1 as a critical tumor intrinsic regulator in controlling the sensitivity of tumor cells to radiotherapy through modulating IR-induced noncanonical NF-κB expression.

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Up-regulation of Krüppel-Like Factor 8 Promotes Tumor Invasion and Indicates Poor Prognosis for Hepatocellular Carcinoma

Cited by 85 publications

References 38 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

Small hairpin RNA-mediated Krüppel-like factor 8 gene knockdown inhibits invasion of nasopharyngeal carcinoma

PELI1 promotes radiotherapy sensitivity by inhibiting noncanonical NF‐κB in esophageal squamous cancer

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