Krüppel-like factor 9 down-regulates matrix metalloproteinase 9 transcription and suppresses human breast cancer invasion

Bai, Xiaoyan; Li, Shujing; Wang, Miao; Li, Xiahui; Yang, Yangyang; Xu, Zhaowei; Li, Bowen; Li, Yanan; Xia, Kangkai; Chen, Huan; Wu, Harry X.

doi:10.1016/j.canlet.2017.10.027

Cited by 67 publications

(77 citation statements)

References 40 publications

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“…Salvador et al reported that LOXL2 was involved in the metastatic process via modifying the ECM stiffness in PyMT tumors. Evidence highlights a dominant role for MMP‐9 in breast cancer invasion as well . These results were in line with our findings that LOXL2 and MMP‐9 functioned as HIF‐2α targets and could mediate the ATP‐driven invasion process.…”

Section: Discussionsupporting

confidence: 91%

Extracellular ATP promotes breast cancer invasion and epithelial‐mesenchymal transition via hypoxia‐inducible factor 2α signaling

et al. 2019

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Extracellular ATP has been shown to play an important role in invasion and the epithelial‐mesenchymal transition (EMT) process in breast cancer; however, the mechanism is unclear. Here, by using a cDNA microarray, we demonstrated that extracellular ATP could stimulate hypoxia‐inducible factor (HIF) signaling and upregulate hypoxia‐inducible factor 1/2α (HIF‐1/2α) expression. After knocking down HIF‐1/2α using siRNA, we found that ATP‐driven invasion and EMT were significantly attenuated via HIF2A‐siRNA in breast cancer cells. By using ChIP assays, we revealed that the biological function of extracellular ATP in invasion and EMT process depended on HIF‐2α direct targets, among which lysyl oxidase‐like 2 (LOXL2) and matrix metalloproteinase‐9 (MMP‐9) mediated ATP‐driven invasion, and E‐cadherin and Snail mediated ATP‐driven EMT, respectively. In addition, using silver staining and mass spectrometry, we found that phosphoglycerate kinase 1 (PGK1) could interact with HIF‐2α and mediate ATP‐driven HIF‐2α upregulation. Furthermore, we demonstrated that expressions of HIF‐2α and its target proteins could be regulated via ATP by AKT‐PGK1 pathway. Using a Balb/c mice model, we illustrated the function of HIF‐2α in promoting tumor growth and metastasis in vivo. Moreover, by exploring online databases, we found that molecules involved in ATP‐HIF‐2α signaling were highly expressed in human breast carcinoma tissues and were associated with poor prognosis. Altogether, these findings suggest that extracellular ATP could promote breast carcinoma invasion and EMT via HIF‐2α signaling, which may be a potential target for future anti–metastasis therapy.

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Section: Discussionsupporting

confidence: 91%

Extracellular ATP promotes breast cancer invasion and epithelial‐mesenchymal transition via hypoxia‐inducible factor 2α signaling

et al. 2019

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“…MMPs are abundantly detected in numerous malignant neoplasms and have critical implications in almost all stages of tumour progression [2]. Recent studies have shown that aberrant MMP expression is associated with the invasion and metastasis of several malignant tumours (colorectal [3], prostate [4], liver [5], breast [6], retinoblastoma [7], and lung [8]) both in vitro and vivo. Among the MMPs, MMP7 (aka matrilysin1) is the smallest secreted proteolytic enzyme, lacking the C-terminal hemopexin domain compared with other family members, with a wide spectrum of substrate specificity against ECM components, including laminin, type IV collagen, fibronectin, and proteoglycans [9,10], as well as other molecules, such as E-cadherin, β4 integrin, tumour necrosis factor-α, and the Fas ligand [11].…”

Section: Introductionmentioning

confidence: 99%

Elevated matrix metalloproteinase 7 expression promotes the proliferation, motility and metastasis of tongue squamous cell carcinoma

et al. 2020

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Background: Matrix metalloproteinase 7 (MMP7), as the smallest member of the matrix metalloproteinase family, has been verified to be implicated in cancer progression, especially metastasis. However, its expression pattern and function in tongue cancer is not clear. Methods: The expression of MMP7 in human tongue squamous cell carcinoma (TSCC) specimens compared with their respective paired nontumour tissues by real-time PCR and immunohistochemical staining. The effect of MMP7 on the proliferation, apoptosis, migration, invasion of tongue cancer cells was tested in appropriate ways after MMP7 siRNA knockdown or overexpression. The effect of MMP7 on lymph node metastasis in vivo was analyzed using a high-metastasis orthotopic nude mouse tongue transplanted tumour model. Results: We found markedly elevated expression of MMP7 in human TSCC specimens compared with their respective paired nontumour tissues, and this high expression was correlated with the patients' lymph node metastasis. Furthermore, the results of molecular functional assays confirmed that MMP7 promotes cell proliferation, migration and invasion of TSCC cells. Knockdown of MMP7 inhibited lymph nodes metastasis in vivo. Conclusions: MMP7 plays an oncogenic role in carcinogenesis and metastasis of tongue cancer, and may serve as a potential therapeutic target for tongue cancer.

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“…27,28 The promoter region of the MMP-9 gene contains the binding site of NF-kB; therefore, MMP-9 expression decreases when NF-kB is suppressed. 29,30 Also, some reports argue that NF-kB suppresses MMP-2 expression. 31e34 Few reports, however, focus on the molecular mechanisms between NF-kB and MMP-2.…”

Section: Discussionmentioning

confidence: 99%

Prevention of early liver metastasis after pancreatectomy by perioperative administration of a nuclear factor-κB inhibitor in mice

Saito

Uwagawa

Hamura

et al. 2019

Surgery

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Background: Liver metastasis is a common problem after pancreatectomy for pancreatic cancer. In pancreatic cancer cells, nuclear factor-kB is activated constitutively. Nuclear factor-kB activates matrix metalloproteinase-2/9, which plays an important role in cancer metastasis. Because the serine protease inhibitor FUT-175 suppresses nuclear factor-kB, we hypothesized that perioperative treatment with FUT-175 for pancreatic cancer may help to prevent liver metastasis. Methods: We compared in vitro cell viability, cell invasiveness, nuclear factor-kB signaling, and the expression levels of matrix metalloproteinase signals between the control group (C group) and the FUT-175 group (F group) using the murine pancreatic cancer cells PAN02. In addition, we evaluated the in vivo effect of pretreatment with FUT-175 using an established model of liver metastasis in mice. Metastatic liver lesions were assessed with magnetic resonance imaging. Liver recurrence and overall survival were evaluated. Also, the antimetastatic effect of systemic administration of FUT-175 was examined. Results: FUT-175 did not suppress the cell viability of PAN02 cells at or after 24 hours of treatment (P > .05); however, cell invasion was suppressed in the F group compared with the C group (P < .05). The levels of nuclear factor-kB activation, membrane type-1 (MT-1) matrix metalloproteinase (MMP)/ matrix metalloproteinase-14 (MMP-14), and matrix metalloproteinase-2/9 (MMP-2/9) were lower in the F group compared with the C group. In vivo, both disease-free and overall survivals were prolonged in the F group compared with the C group. Systemic administration was also effective in suppressing the number of metastases. Conclusion: Perioperative treatment with FUT-175 may help to prevent early liver metastasis after pancreatectomy for pancreatic cancer.

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Krüppel-like factor 9 down-regulates matrix metalloproteinase 9 transcription and suppresses human breast cancer invasion

Cited by 67 publications

References 40 publications

Extracellular ATP promotes breast cancer invasion and epithelial‐mesenchymal transition via hypoxia‐inducible factor 2α signaling

Extracellular ATP promotes breast cancer invasion and epithelial‐mesenchymal transition via hypoxia‐inducible factor 2α signaling

Elevated matrix metalloproteinase 7 expression promotes the proliferation, motility and metastasis of tongue squamous cell carcinoma

Prevention of early liver metastasis after pancreatectomy by perioperative administration of a nuclear factor-κB inhibitor in mice

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