Raf kinase inhibitor protein inhibits cholangiocarcinoma cell metastasis by downregulating matrix metalloproteinase 9 and upregulating tissue inhibitor of metalloproteinase 4 expression

Ma, Junwei; Shi, Jin; Zhao, Dongqiang; Cheng, Lijuan; Wang, Wenbin; Li, Fangfang; Jiang, Xiaoyu; Jiang, Huiqing

doi:10.3892/ol.2014.2637

Cited by 14 publications

(7 citation statements)

References 31 publications

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“…RKIP-expressing cells had reduced MMP levels and upregulated tissue inhibitor of metalloproteinases levels. 14 Likewise, RKIP considerably inhibited the invasive and metastasizing potential of esophageal cancer cells via the downregulation of MMP14. 15 Increased expression of RKIP has also been reported to inhibit the distantly metastasizing potential of advanced nasopharyngeal carcinoma cells.…”

Section: The Crosstalk Of Rkip With Other Proteinsmentioning

confidence: 98%

The biological complexity of RKIP signaling in human cancers

Farooqı

Sarkar

2015

Exp Mol Med

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The Raf kinase inhibitory protein (RKIP) has been demonstrated to modulate different intracellular signaling pathways in cancers. Studies have shown that RKIP is frequently downregulated in cancers; therefore, attempts have been made to upregulate the expression of RKIP using natural and synthetic agents for the treatment of human malignancies. Moreover, various regulators such as specific proteins and microRNAs (miRNAs) that are involved in the regulation of RKIP expression have also been identified. RKIP mechanistically modulates the apoptotic regulators of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling. Because of its critical role in human cancers, RKIP has drawn much research attention, and our understanding is expanding rapidly. Here, we summarize some of the biological complexities of RKIP regulation. However, we restrict our discussion to selected tumors by focusing on TRAIL, miRNAs and natural agents. Emerging evidence suggests a role for natural agents in RKIP regulation in cancer cells; therefore, naturally occurring agents may serve as cancer-targeting agents for cancer treatment. Although the literature suggests some advancement in our knowledge of RKIP biology, it is incomplete with regard to its preclinical and clinical efficacy; thus, further research is warranted. Furthermore, the mechanism by which chemotherapeutic drugs and novel compounds modulate RKIP and how nanotechnologically delivered RKIP can be therapeutically exploited remain to be determined.

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Section: The Crosstalk Of Rkip With Other Proteinsmentioning

confidence: 98%

The biological complexity of RKIP signaling in human cancers

Farooqı

Sarkar

2015

Exp Mol Med

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“…For example, RKIP mediates overall restriction of cell motility by downregulating matrix metalloproteinases (MMPs), which degrade components of the extracellular matrix during EMT. 164,165 RKIP also reduces mRNA and protein expressions of cellular adhesion molecules—vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1)—which facilitate cell migration and metastasis. 166 The NF-κB/Snail/YY1/RKIP/PTEN circuit dictates EMT-related gene expression and chemo-immuno-resistance in tumor cells.…”

Section: Raf-1 Kinase Inhibitory Proteinmentioning

confidence: 99%

A New Linkage between the Tumor Suppressor RKIP and Autophagy: Targeted Therapeutics

Wang

Bonavida

2018

Crit Rev Oncog

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The complexities of molecular signaling in cancer cells have been hypothesized to mediate cross-network alterations of oncogenic processes such as uncontrolled cell growth, proliferation, acquisition of epithelial-to-mesenchymal transition (EMT) markers, and resistance to cytotoxic therapies. The two biochemically exclusive processes/proteins examined in the present review are the metastasis suppressor Raf-1 kinase inhibitory protein (RKIP) and the cell-intrinsic system of macroautophagy (hereafter referred to as autophagy). RKIP is poorly expressed in human cancer tissues, and low expression levels are correlated with high incidence of tumor growth, metastasis, poor treatment efficacy, and poor prognoses in cancer patients. By comparison, autophagy is a conserved cytoprotective degradation pathway that has been shown to influence the acquisition of resistance to hypoxia and nutrient depletion as well as the regulation of chemoimmuno-resistance and apoptotic evasion. Evidently, a broad library of cancer-relevant studies exists for RKIP and autophagy, although reports of the interactions between pathways involving RKIP and autophagy have been relatively sparse. To circumvent this limitation, the coordinate regulatory and effector mechanisms were examined for both RKIP and autophagy. Here, we propose three putative pathways that demonstrate the inherent pleiotropism and relevance of RKIP and the microtubule-associated protein 1 light chain 3 (MAP1LC3, LC3) on cell growth, proliferation, senescence, and EMT, among the hallmarks of cancer. Our findings suggest that signaling modules involving p53, signal transducer and activator of transcription 3 (STAT3), nuclear factor-κB (NF-κB), and Snail highlight the novel roles for RKIP in the control of autophagy and vice versa. The suggested potential crosstalk mechanisms are new areas of research in which to further study RKIP and autophagy in cancer models. These should lead to novel prognostic motifs and will provide alternative therapeutic strategies for the treatment of unresponsive aggressive cancer types.

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“…Invasive pituitary adenoma has a complicated mechanism and interacts with the nerve-endocrine-immune network. It is affected by a variety of factors, not only genes, but also ECM [ 16 , 17 ]. ECM plays a physiological role in normal pituitary tissues.…”

Section: Discussionmentioning

confidence: 99%

Effect of Hypoxia on DDR1 Expression in Pituitary Adenomas

Zhang

Xue

et al. 2015

Med Sci Monit

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BackgroundPituitary adenoma is a common intracranial tumor in neurosurgery. Some pituitary adenomas have the characteristics of invasive growth make them unable to be removed completely by surgery leading to easy relapse. Discoidin domain receptor l (DDR1) is a new kind of tyrosine kinase receptor on the cell surface. DDR1 can be activated by tumor microenvironment signal in tumorigenesis, increasing MMP-2/9 expression and promoting the invasive ability of tumor cells. Anoxia can promote tumor growth and metastasis. This study investigated the impact of anoxic environment DDR1 expression in pituitary adenoma.Material/MethodsA primary hypoxia pituitary adenoma cell model was established and treated with DDR1 inhibitor nilotinib. Real-time PCR and Western blot were used to detect DDR1 mRNA and protein expression. ELISA was used to detect MMP-2/9 changes. MTT method was used to detect pituitary adenoma cell proliferation. We used a transwell chamber to determine pituitary adenoma cell invasion ability.ResultsDDR1 mRNA and protein were significantly overexpressed under hypoxia (P<0.05). MMP-2 and MMP-9 expression was obviously increased in supernatant (P<0.05). Pituitary adenoma cell proliferation and invasive ability improved markedly under hypoxia (P<0.05). Nilotinib could reduce DDR1 expression, decrease MMP-2 and MMP-9 expression, and inhibit pituitary adenoma cells proliferation and invasion.ConclusionsHypoxia can increase DDR1 expression in pituitary adenoma cells, leading to improved MMP-2 and MMP-9 secretion, and promoting pituitary adenoma cell proliferation and invasion.

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Raf kinase inhibitor protein inhibits cholangiocarcinoma cell metastasis by downregulating matrix metalloproteinase 9 and upregulating tissue inhibitor of metalloproteinase 4 expression

Cited by 14 publications

References 31 publications

The biological complexity of RKIP signaling in human cancers

The biological complexity of RKIP signaling in human cancers

A New Linkage between the Tumor Suppressor RKIP and Autophagy: Targeted Therapeutics

Effect of Hypoxia on DDR1 Expression in Pituitary Adenomas

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