DLC-1, a candidate tumor suppressor gene, inhibits the proliferation, migration and tumorigenicity of human nasopharyngeal carcinoma cells

Feng, Xiangling; Li, Cui; Liu, Weidong; Chen, Huan; Zhou, Wen; Wang, Lei; Zhu, Bin; Yao, Kai-Tai; Jiang, Xingjun; Ren, Chao

doi:10.3892/ijo.2013.1885

Cited by 21 publications

(31 citation statements)

References 38 publications

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“…Meanwhile, MMPs can induce EMT by modulating the conformation of E-cad, which results in the release of extracellular domain of E-cad, and increasing the Snail expression [10,37,38]. Previously, we and other groups have confirmed that DLC-1 can inhibit the migration of cancers [4,5,31]; however, studies focusing on the relation between DLC-1 and MMPs are extremely rare. Here, for the first time again, we showed that DLC-1 can inhibit the expressions of MMPs in NPC reflecting downregulated MMP-2, MMP-7, MMP-9 expressions in 5-8F-DLC-1 cells which illustrated the negative regulation of DLC-1 on NPC metastasis in accordance to our previous work [5].…”

Section: Discussionmentioning

confidence: 91%

“…Cell culture 5-8F-DLC-1 cell line with forced expression of DLC-1 in 5-8F cells and 5-8F-vector cell line, served as control, was established in the previous work [5]. And they were cultured in RPMI-1640 (Life Technologies, CA, USA) supplemented with 10 % newborn calf serum (BI, Beit-Haemek, Israel) and 100 lg/ml geneticin (Life Technologies, CA, USA) under 37°C in a humidified 5 % CO 2 incubator.…”

Section: Methodsmentioning

confidence: 99%

“…Among these, EGFR-related signaling has a central role in the development and progression of different carcinomas [19,20]. In our previous study, the inhibited expression of EGFR in 5-8F-DLC-1 cells was detected and validated by microarray analysis and reverse transcription polymerase chain reaction, respectively [5]. So, additional efforts were devoted to clarify the functions of EGFR in 5-8F-DLC-1 cells.…”

Section: Inhibition Of Egfr/akt/nf-jb Signaling May Account For the Smentioning

confidence: 97%

“…Ectopic expression of DLC-1 can induce apoptosis and inhibit proliferation, migration, invasion as well as metastasis in cancers of different tissue origins such as lung, liver, pancreas and nasopharynx. [3][4][5][6]. DLC-1 belongs to the GTPase-activating protein (GAP) family and can negatively regulate Rho GTPase to avoid the hyper-activation of signaling conduction which may lead to malignant transformation at last [4].…”

Section: Introductionmentioning

confidence: 99%

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DLC-1 induces mitochondrial apoptosis and epithelial mesenchymal transition arrest in nasopharyngeal carcinoma by targeting EGFR/Akt/NF-κB pathway

et al. 2015

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Loss of deleted in liver cancer-1 (DLC-1) can induce apoptosis and inhibit the mobility, migration and metastasis in several cancers. Previously, we revealed that ectopic expression of DLC-1 can suppress proliferation, mobility, migration and tumorigenesis in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms accounting for the roles of DLC-1 in NPC are still obscure. In the present work, we attempted to study and uncover the mechanisms underlying the functions of DLC-1 in NPC. The apoptosis of 5-8F-DLC-1 cells, established previously, was analyzed by mitochondrial membrane potentials assay and flow cytometer analysis. And the antibodies involving pathways such as mitochondrial-associated apoptosis, epithelial mesenchymal transition and metastasis were applied to detect and compare the expression level of targeted proteins. The obvious apoptosis of 5-8F-DLC-1 cells was observed reflected by mitochondrial depolarization and lower ratio in cell viability. Subsequently, the activation of mitochondrial apoptosis was verified by the increased expressions of Bax, Apaf1, cleave-caspases and cleave-PARP, etc, and the decreased expressions of Bcl-2, Bcl-xL, Mcl-1, Survivin, etc, in 5-8F-DLC-1 cells. Then, the inhibited epithelial mesenchymal transition of 5-8F-DLC-1 cells was validated by upregulated expression of E-cadherin and downregulated expression of N-cadherin, Snail, Vimentin. Subsequently, downregulated expressions of proteins such as FAK, RhoA, ROCK1 and cdc25 related to cell adhesion and cytoskeleton organization were also observed. And expressions of MMPs were inhibited in 5-8F-DLC-1 cells. At last, the inhibited activity of EGFR/Akt/NF-κB axis was revealed by the decreased expressions of phosho-EGFR, phosho-Akt, phosho-p38MAPK, phosho-IKKα and phosho-p65. Here, we systematically explored the mechanisms underlying the negative roles of DLC-1 in NPC cells. For the first time, we confirmed that the ectopic expression DLC-1 can induce mitochondrial apoptosis, inhibit EMT and related processes by targeting the EGFR/Akt/NF-κB pathway, which, beyond all doubt, offered beneficial guidelines for other studies and laid a good foundation for its clinical applications ultimately.

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Section: Discussionmentioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Inhibition Of Egfr/akt/nf-jb Signaling May Account For the Smentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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DLC-1 induces mitochondrial apoptosis and epithelial mesenchymal transition arrest in nasopharyngeal carcinoma by targeting EGFR/Akt/NF-κB pathway

et al. 2015

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“…Colony formation assay was performed as described earlier (19). First, 5-8F and 6-10B cells were treated with 5 mM NaBu for 48 h. Then, the treated cells were trypsinized and seeded in 6-well plates at a density of 1,000 cells/well.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of store-operated Ca2+ entry counteracts the apoptosis of nasopharyngeal carcinoma cells induced by sodium butyrate

Huang¹,

Ren²,

Huang³

et al. 2016

Oncology Letters

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Abstract. Sodium butyrate (NaBu), a histone deacetylase inhibitor, has demonstrated anti-tumor effects in several cancers, and is a promising candidate chemotherapeutic agent. However, its roles in nasopharyngeal carcinoma (NPC), an endemic malignant disease in Southern China and Southeast Asia, has rarely been studied. In the present study, MTT assay, colony formation assay, flow cytometry analysis and western blotting were performed to explore the influence of NaBu on NPC cells and its underlying mechanism. NaBu induced morphological changes and inhibited proliferation in 5-8F and 6-10B cells. MTT assay revealed that NaBu was cytotoxic to 5-8F and 6-10B cells in a dose-and time-dependent manner. Furthermore, flow cytometry analysis revealed that NaBu induced obvious cell apoptosis in 5-8F and 6-10B cells due to the activation of the mitochondrial apoptosis axis. In addition, flow cytometry analysis and western blotting demonstrated that NaBu could enhance the Ca 2+ influx by promoting store-operated Ca 2+ entry (SOCE) in 5-8F and 6-10B cells. Inhibition of SOCE by specific inhibitors or downregulated expression of calcium release-activated calcium channel protein 1 and stromal interaction molecule 1 could counteract the apoptosis of NPC cells induced by NaBu. Thus, the current study revealed that enhanced SOCE and activated mitochondrial apoptosis axis may account for the mechanisms of cytotoxicity of NaBu in NPC cells, and that NaBu serves as a promising chemotherapeutic agent in NPC therapy.

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Knockdown Rab11‐FIP2 inhibits migration and invasion of nasopharyngeal carcinoma via suppressing Rho GTPase signaling

Feng

Qin

Liao

et al. 2019

J of Cellular Biochemistry

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Rab11 family interacting protein 2 (Rab11‐FIP2) is a conserved protein and effector molecule for the small GTPase Rab11. By interacting with Rab11 and MYO5B, Rab11‐FIP2 regulates endosome trafficking of plasma membrane proteins, promoting cellular motility. The endosomal trafficking system in nasopharyngeal carcinoma (NPC) remains unclear. Here, an outlier analysis using the Oncomine database suggested that Rab11‐FIP2 but not Rab11 and MYO5B was overexpressed in NPC. We confirmed that the transcription of Rab11‐FIP2 was upregulated in NPC cell lines and primary tumor tissues as compared with a normal nasopharyngeal epithelial cell line and normal nasopharynx tissues. We further confirmed the elevated protein expression level of Rab11‐FIP2 in NPC biopsies. Instead of regulating the epithelial‐mesenchymal transition or Akt signaling pathway, knockdown of Rab11‐FIP2 inhibited the migration and invasion ability of NPC cell lines by decreasing the expression of Rac and Cdc42. In summary, Rab11‐FIP2 could be an oncogene in NPC, mainly contributing to metastatic capacity by activating Rho GTPase signaling.

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DLC-1, a candidate tumor suppressor gene, inhibits the proliferation, migration and tumorigenicity of human nasopharyngeal carcinoma cells

Cited by 21 publications

References 38 publications

DLC-1 induces mitochondrial apoptosis and epithelial mesenchymal transition arrest in nasopharyngeal carcinoma by targeting EGFR/Akt/NF-κB pathway

DLC-1 induces mitochondrial apoptosis and epithelial mesenchymal transition arrest in nasopharyngeal carcinoma by targeting EGFR/Akt/NF-κB pathway

Inhibition of store-operated Ca2+ entry counteracts the apoptosis of nasopharyngeal carcinoma cells induced by sodium butyrate

Knockdown Rab11‐FIP2 inhibits migration and invasion of nasopharyngeal carcinoma via suppressing Rho GTPase signaling

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