Krüppel-like Factor 4 Induces <i>p27Kip1</i> Expression in and Suppresses the Growth and Metastasis of Human Pancreatic Cancer Cells

Wei, Daoyan; Kanai, Masahsi; Jia, Zhiliang; Xin, Le; Xie, Keping

doi:10.1158/0008-5472.can-07-5953

Cited by 132 publications

(146 citation statements)

References 46 publications

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“…Recently, KLF4 has been shown to inhibit cell migration and invasion in TE2 of human ESCC cell line (28). In addition, KLF4 can inhibit pancreatic cancer metastasis in vivo (23). Consistent with these results, KLF4 overexpression reduces cell migration and invasion in RKO colon cancer cells (29).…”

Section: Discussionsupporting

confidence: 59%

“…In line with these studies, the loss of KLF4 expression has been reported in several human tumors, including colorectal, stomach, esophageal, and bladder cancers (22)(23)(24)(25), which indicates its tumor suppressor role. However, KLF4 also exhibits oncogenic properties.…”

supporting

confidence: 66%

“…Overexpression of KLF4 could be detected in oropharynx (26) and mammary carcinomas (27). Moreover, it has been reported to inhibit metastasis of several cancers, including esophageal (28), pancreatic (23), and colorectal cancer cells (29). In addition, KLF4 mRNA is targeted by miR-145 (30), implicating the post-transcriptional control of KLF4.…”

mentioning

confidence: 99%

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MicroRNA-10b Promotes Migration and Invasion through KLF4 in Human Esophageal Cancer Cell Lines

Tian

Luo

Cai

et al. 2010

Journal of Biological Chemistry

275

207

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Recently, microRNAs have emerged as regulators of cancer metastasis through acting on multiple signaling pathways involved in metastasis. In this study, we have analyzed the level of miR-10b and cell motility and invasiveness in several human esophageal squamous cell carcinoma cell lines. Our results reveal a significant correlation of miR-10b level with cell motility and invasiveness. Overexpression of miR-10b in KYSE140 cells increased cell motility and invasiveness, whereas inhibition of miR-10b in EC9706 cells reduced cell invasiveness, although it did not alter cell motility. Additionally, we identified KLF4, a known tumor suppressor gene that has been reported to suppress esophageal cancer cell migration and invasion, as a direct target of miR-10b. MicroRNAs, a class of small noncoding RNAs, have been identified as a new kind of gene expression regulators through targeting mRNAs for translational repression or cleavage (1-3). Lately, emerging evidence suggests important roles for miRNAs 2 in apoptosis (4), hematopoietic development (5), cell proliferation (6), skin morphogenesis (7), and neural development (8). Deregulation of miRNAs has also been reported in a variety of tumors, including breast cancer, leukemia, lung cancer, and colon cancer (9 -11), which indicated a significant correlation between miRNAs and human malignancy. miRNA expression profiling in esophageal cancers revealed a distinct miRNA signature (12, 13), and some miRNAs showed correlation with several clinicopathologic parameters (13). Furthermore, miR-21 is reported to regulate the proliferation and invasion in ESCC (14), and the miR-106b-25 polycistron is activated by genomic amplification and is potentially involved in esophageal neoplastic progression (15), providing evidence of a causal role for miRNAs in esophageal cancer development.Recent studies show that miRNAs may act as activators or inhibitors of tumor metastasis by acting on multiple signaling pathways involved in metastasis (16 -18). Ma et al. (16) found that miR-10b initiates invasion and metastasis in breast cancer. miR10b, induced by the prometastatic transcription factor TWIST1, proceeds to inhibit translation of mRNA of HOXD10, a transcription factor already known for its roles in cell motility (19), resulting in increased expression of a pro-metastatic gene, RHOC. This study has provided the first evidence for a role of miRNA in tumor metastasis. Subsequently several additional miRNAs have been reported to act on various steps of metastasis (17, 18).Krüppel-like factor 4 (KLF4), a zinc finger protein of the Krüp-pel-like factor family, plays a role in cell cycle regulation, differentiation, and rises in response to DNA damage, serum starvation, and contact inhibition (20, 21). In line with these studies, the loss of KLF4 expression has been reported in several human tumors, including colorectal, stomach, esophageal, and bladder cancers (22-25), which indicates its tumor suppressor role. However, KLF4 also exhibits oncogenic properties. Overexpression of KLF4 could b...

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Section: Discussionsupporting

confidence: 59%

supporting

confidence: 66%

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MicroRNA-10b Promotes Migration and Invasion through KLF4 in Human Esophageal Cancer Cell Lines

Tian

Luo

Cai

et al. 2010

Journal of Biological Chemistry

275

207

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“…[24][25][26][27][28][29][30] The lack of KLF4 expression has previously been reported in other types of tumors, especially in large bowel and gastric adenocarcinomas, [31][32][33] and it has also been associated with an aggressive evolution in gastric cancer. 33 Likewise, suppression of growth and metastasis in human pancreatic cancer cells by KLF4 expression has been described, 34 suggesting that it may behave as a suppressor gene. Conversely, and in contrast to the consideration of KLF4 as a tumor suppressor protein, 3 laboratories have identified it as a potential oncogene.…”

Section: 23mentioning

confidence: 99%

Alterations in the Expression of p53, KLF4, and p21 in Neuroendocrine Lung Tumors

Gómez

Bernal

Arranz

et al. 2014

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Neuroendocrine lung neoplasms are a heterogeneous group of tumors with different clinical behavior and prognosis.Objectives.-To evaluate the expression of p53, KLF4, and p21 in neuroendocrine lung neoplasms and to analyze the influence that expression has on the prognosis of those tumors.Design.-All neuroendocrine lung neoplasms (N ¼ 109) resected in our institution were reviewed, with the collection of histologic slides and paraffin blocks of 47 typical carcinoids (43%), 9 atypical carcinoids (8%), 35 large cell neuroendocrine carcinomas (32%), and 18 small cell lung carcinomas (17%), as well as 10 tumorlets (100%). Four tissue microarrays were performed. Followup was assessed in all cases (119 of 119; 100%).Results.-p53 protein immunostaining results were negative in both the tumorlets and typical carcinoids and were overexpressed in 11% (1 of 9) of the atypical carcinoids and in 68% (36 of 53) of the carcinomas. KLF4 results were positive in all tumorlets (10 of 10; 100%), 32% (15 of 47) of the typical carcinoids, 44% (4 of 9) of the atypical carcinoids, and 62% (33 of 53) of the carcinomas. p21 expression did not differ among the groups. The lack of KLF4 and p21 expression was associated with an accumulation of aggressive features in typical carcinoids (P ¼ .04 and P ¼ .004, respectively, Fisher exact test).Conclusions.-p53, KLF4, and p21 showed altered expression patterns in pulmonary neuroendocrine neoplasms. Lack of KLF4 and p21 expression was associated with accumulation of aggressive features in typical carcinoids.(

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“…Negative regulation of KLF4 by Notch signalling has been observed in intestinal epithelium or colorectal cancer cells 37,38 and these results are in favour of the tumour suppressor role of KLF4 in colorectal cancer cells 39 . In contrast to the tumour suppressor role of KLF4 in colorectal cancer cells/intestinal epithelium and pancreatic cancer [37][38][39][40][41] , other groups have demonstrated the oncogenic role of KLF4 in breast cancer and HNC [42][43][44] . These findings are consistent with our discovery that KLF4 plays an oncogenic role, especially in HNSCC 44 .…”

Section: Oecm1-twist1mentioning

confidence: 98%

Twist1 induces endothelial differentiation of tumour cells through the Jagged1-KLF4 axis

et al. 2014

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The mechanisms controlling tumour-induced angiogenesis are presently not clear. In principle, angiogenesis can be achieved through the activation of endothelial cells in existing vessels or by transdifferentiation of tumour cells into endothelial cells. However, whether tumour cells can go through a prior epithelial-mesenchymal transition and further differentiate into endothelial cells remains unknown. Here we show that overexpression of Twist1, a transcriptional regulator that induces and promotes cancer metastasis, leads to endothelial differentiation in head and neck cancer (HNC) cells. Induction of Jagged1 expression by Twist1 is essential for Twist1-induced endothelial differentiation. The Jagged1/ Notch signalling subsequently activates KLF4, inducing stem-like properties in HNC cells and conferring them with drug resistance. Our results indicate that the Twist1-Jagged1/KLF4 axis is essential both for transdifferentiation of tumour cells into endothelial cells and for chemoresistance acquisition.

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Krüppel-like Factor 4 Induces p27Kip1 Expression in and Suppresses the Growth and Metastasis of Human Pancreatic Cancer Cells

Cited by 132 publications

References 46 publications

MicroRNA-10b Promotes Migration and Invasion through KLF4 in Human Esophageal Cancer Cell Lines

MicroRNA-10b Promotes Migration and Invasion through KLF4 in Human Esophageal Cancer Cell Lines

Alterations in the Expression of p53, KLF4, and p21 in Neuroendocrine Lung Tumors

Twist1 induces endothelial differentiation of tumour cells through the Jagged1-KLF4 axis

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