KiSS1 inhibits growth and invasion of osteosarcoma cells through inhibition of the MAPK pathway

Zhang, Y.; Tang, Yan; Li, Z.H.; Pan, Feng; Huang, Kuan Lin; Xu, G.

doi:10.4081/ejh.2013.e30

Cited by 21 publications

(11 citation statements)

References 27 publications

(26 reference statements)

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“…Zhang et al . reported that KiSS1 functioned as a tumor suppressor in osteosarcoma cells through inhibition of the MAPK pathway 34 . In addition, Li et al .…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of RPS9 Inhibits Osteosarcoma Cell Growth through Inactivation of MAPK Signaling Pathway

Cheng

Zhu

et al. 2017

J. Cancer

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Objectives: Osteosarcoma is the most common malignant bone tumor in adolescents; however, the mechanisms involved in the pathogenesis and progression of osteosarcoma remain to be elucidated. Researchers have provided valuable insights into the tumorigenesis of Ribosomal protein S9 (RPS9) in some cancers. The purpose of this study was to elucidate the expression, functions, and mechanisms of RPS9 in human osteosarcoma. Methods: The expression of RPS9 in osteosarcoma tissues and cell lines was evaluated by qRT-PCR and western blotting. Knockdown of RPS9 induced by RNA interference (RNAi) method in three osteosarcoma cell lines (MNNG/HOS, MG63, and U2OS) was employed to analyze the effects of RPS9 on cell proliferation and cell cycle distribution. The host signaling pathways affected by RPS9 were detected using the intracellular signaling antibody array kit PathScan®. Results: The expression of RPS9 was found to be up-regulated in human osteosarcoma tissues and cell lines. Its expression was positively correlated with Enneking stage and the tumor recurrence. Down-regulation of RPS9 inhibited osteosarcoma cell proliferation, colony-forming ability, and cell cycle G1 phase in vitro. In addition, our data demonstrated that knockdown of RPS9 repressed the protein levels of phospho-SAPK/JNK and phospho-p38. Conclusion: RPS9 is up-regulated and has a pro-tumor effect in osteosarcoma through the activation of MAPK signaling pathway and thus can be used as a potential target for gene therapy.

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“…Zhang et al . reported that KiSS1 functioned as a tumor suppressor in osteosarcoma cells through inhibition of the MAPK pathway 34 . In addition, Li et al .…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of RPS9 Inhibits Osteosarcoma Cell Growth through Inactivation of MAPK Signaling Pathway

Cheng

Zhu

et al. 2017

J. Cancer

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“…MMP-9 can release factors sequestered in the extracellular matrix, including VEGF, TGF-β and FGF-2, and stimulate proliferation and migration of endothelial cells [ 38 , 41 ]. It is evidenced that KiSS-1 can suppress MMP-9 expression [ 42 ]; we therefore tested whether our expressed protein had such activity. The results firmly confirmed that KiSS1 secreted from our recombinant L. lactis NZ9000-pNZ401-KiSS1 strain effectively downregulated the expression of MMP-9.…”

Section: Discussionmentioning

confidence: 99%

Recombinant Lactococcus lactis NZ9000 secretes a bioactive kisspeptin that inhibits proliferation and migration of human colon carcinoma HT-29 cells

Zhang

Zuo

et al. 2016

Microb Cell Fact

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BackgroundProteinaceous bioactive substances and pharmaceuticals are most conveniently administered orally. However, the facing problems are the side effects of proteolytic degradation and denaturation in the gastrointestinal tract. In recent years, lactic acid bacteria (LAB) have been verified to be a promising delivery vector for susceptible functional proteins and drugs. KiSS-1 peptide, a cancer suppressor, plays a critical role in inhibiting cancer metastasis and its activity has been confirmed by direct administration. However, whether this peptide can be functionally expressed in LAB and exert activity on cancer cells, thus providing a potential alternative administration manner in the future, has not been demonstrated.ResultsA recombinant Lactococcus lactis strain NZ9000-401-kiss1 harboring a plasmid containing the gene of the tumor metastasis-inhibiting peptide KiSS1 was constructed. After optimization of the nisin induction conditions, the recombinant strain efficiently secreted KiSS1 with a maximum detectable amount of 27.9 μg/ml in Dulbecco’s Modified Eagle medium. The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide and would healing assays, respectively, indicated that the secreted KiSS1 peptide remarkably inhibited HT-29 cell proliferation and migration. Furthermore, the expressed KiSS1 was shown to induce HT-29 cell morphological changes, apoptosis and reduce the expression of matrix metalloproteinase 9 (MMP-9) at both mRNA and protein levels.ConclusionsA recombinant L. lactis NZ9000-401-kiss1 successfully expressing the human kiss1 was constructed. The secreted KiSS1 peptide inhibited human HT-29 cells’ proliferation and migration probably by invoking, or mediating the cell-apoptosis pathway and by down regulating MMP-9 expression, respectively. Our results suggest that L. lactis is an ideal cell factory for secretory expression of tumor metastasis-inhibiting peptide KiSS1, and the KiSS1-producing L. lactis strain may serve as a new tool for cancer therapy in the future.

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“…Some groups used DNA microarray analysis to identify a cohort of 13 genes with elevated expression levels in the metastatic osteosarcoma samples when compared to primary tumors [ 23 , 24 ]. Among all those candidate genes, CD73 and IRF4 are closely related to the anti-oxidation of osteosarcoma cells and activation of lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

“…A study in the animal model using DNA microarray analysis found 7 genes with significant expressional variations between higher metastatic and lower metastatic sub-groups of osteosarcoma cells. Some of those genes are correlated with the proliferation and invasion ability of tumors [ 23 , 24 ]. Past studies reported that PMP22 mainly exerted its functions in the motor-sensory neuropathy [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

The Functional Role of PMP22 Gene in the Proliferation and Invasion of Osteosarcoma

Liu

Chen

2015

Med Sci Monit

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BackgroundAs the most common primary bone tumor, osteosarcoma has an improved survival rates with advancement of treatment methods. A higher rate of metastasis, however, leads to the aggravation of the disease. Studies have shown that some genes, namely osteosarcoma metastasis-related genes, participate in the process of tumor metastasis. The peripheral myelin protein 22 (PMP22) gene has recently been found to be abundantly expressed in the oncogenesis of osteosarcoma. Its detailed role and function in the tumor metastasis, however, remains unknown.Material/MethodsThe recombinant retroviral plasmid pcDNA3.1-PMP22 was constructed and used to transfect osteosarcoma cells SOSP-M, whose cell proliferation was measured by MTT method. The formation of tumor cell colony, the cell migration and invasion were also measured. The signal transduction pathway MAPK was further analyzed by Western blotting.ResultsThe pcDNA3.1-PMP22 plasmid was confirmed to have a 305bp PMP22 fragment by EcoRI-XhoI dual digestion. Compared to the control group, osteosarcoma cell invasion was significantly facilitated by the transfection of pcDNA3.1-PMP22 plasmid (p<0.05). The recombinant plasmid also significantly potentiated the formation of tumor cell colony and increased the migration and invasion ability of tumor cells (p<0.05 in all cases). Phosphorylated p-ERK and p-P38 were also up-regulated by vector transfection (p<0.05).ConclusionsOsteosarcoma metastasis-related gene PMP22 participates in the proliferation, invasion, migration and colony formation of osteosarcoma cells possibly via the MAPK signal transduction pathway, providing evidences for further investigation of metastatic mechanism of osteosarcoma.

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KiSS1 inhibits growth and invasion of osteosarcoma cells through inhibition of the MAPK pathway

Cited by 21 publications

References 27 publications

Down-regulation of RPS9 Inhibits Osteosarcoma Cell Growth through Inactivation of MAPK Signaling Pathway

Down-regulation of RPS9 Inhibits Osteosarcoma Cell Growth through Inactivation of MAPK Signaling Pathway

Recombinant Lactococcus lactis NZ9000 secretes a bioactive kisspeptin that inhibits proliferation and migration of human colon carcinoma HT-29 cells

The Functional Role of PMP22 Gene in the Proliferation and Invasion of Osteosarcoma

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