Overexpression of KiSS-1 reduces colorectal cancer cell invasion by downregulating MMP-9 via blocking PI3K/Akt/NF-κB signal pathway

Chen, Shaoqin; Chen, Wei; Zhang, Xiang; Lin, Suyong; Chen, Zhihua

doi:10.3892/ijo.2016.3368

Cited by 51 publications

(38 citation statements)

References 23 publications

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“…Overexpression of KiSS-1 also results in blockade of synthesis of MMP9 and PI3K, as well as the inhibition of phosphorylation of Akt. Furthermore, treatment with PI3K and Akt agonists attenuates the effect of KiSS-1 on the biological activity of CRC cells 24. Taken together, our results suggest that TCF21 induces Kiss-1 expression and subsequently results in downregulation of MMPs and inactivation of PI3K/AKT signaling to exert its inhibitory function on CRC.…”

Section: Discussionsupporting

confidence: 51%

“…Consequently, the reduced synthesis of MMP9 induces certain inhibitory effects on the mobility and invasion of cancer cells 23. In addition, KiSS-1 treatment has been shown to elicit a strong and sustained phosphorylation of ERK1/2 and pAKT 24. Recently, Arab et al25 have found that TCF21 binds the promoter of the melanoma metastasis-suppressing gene, KiSS1 , and enhances its expression through interaction with E12 and with TCF12.…”

Section: Discussionmentioning

confidence: 99%

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TCF21 functions as a tumor suppressor in colorectal cancer through inactivation of PI3K/AKT signaling

Dai¹,

Duan²,

Duan³

et al. 2017

OTT

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Colorectal cancer (CRC) has become a major public health problem, ranking as the third most common type of cancer. Our previous study has revealed that TCF21 is frequently silenced by promoter hypermethylation in both CRC cell lines and primary CRC, with TCF21 methylation being significantly correlated with lymph node invasion. In this study, we further analyze the expression of TCF21 in CRC tissues and investigate the role of TCF21 in CRC in vitro and in vivo. We also explore the possible pathway regulated by TCF21. We thus demonstrate that decreased levels of TCF21 are associated with the pathological stage, clinical stage and lymph node metastasis, indicating a poor prognosis in CRC patients; overexpression of TCF21 inhibits cell proliferation, migration and invasion in the colorectal cell lines HCT116 and HT29. Furthermore, TCF21 functions as a tumor suppressor probably through inactivation of PI3K/AKT signaling and inhibition of MMPs. Our results suggest that enhancement of TCF21 levels may be a potential strategy to facilitate the prevention and treatment of CRC in the clinic.

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

TCF21 functions as a tumor suppressor in colorectal cancer through inactivation of PI3K/AKT signaling

Dai¹,

Duan²,

Duan³

et al. 2017

OTT

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“…Previous studies have reported that Akt/NF-κB signaling pathway was positively correlated with tumor metastasis [20, 21]. To explore whether Akt/NF-κB signaling was also necessary for Tet-induced anti-metastatic effects on 786-O and 769-O cells, Western blotting was then performed.…”

Section: Resultsmentioning

confidence: 99%

“…Also, it has been proven as a regulator of MMP-9 to promote tumor invasion and metastasis [29, 30]. In addition, Akt signaling regulates the expression of NF-κB as well as MMP-9 in several cancer cells [20, 21]. Thus, to elucidate the effect of Tet on activation, Akt/NF-κB signaling was assessed by western blotting.…”

Section: Discussionmentioning

confidence: 99%

Tetrandrine inhibits migration and invasion of human renal cell carcinoma by regulating Akt/NF-κB/MMP-9 signaling

et al. 2017

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Renal cell carcinoma (RCC) is known as one of the most lethal malignancies in the urological system because of its high incidence of metastasis. Tetrandrine (Tet), a traditional Chinese herbal medicine, exerts a potent anti-cancer effect in a variety of cancer cells. However, the anti-metastatic effect of Tet and its possible mechanism in RCC is still unclear. The present study revealed that Tet significantly suppressed the migration and invasion of RCC 786-O and 769-P cells in vitro. Mechanistically, the protein levels of matrix metalloproteinases 9 (MMP-9), phosphorylated PI3K, PDK1, Akt and NF-κB were markedly reduced after Tet treatment. Moreover, co-treatment with LY294002 (PI3K inhibitor) could further enhance the Tet-inhibited migration and invasion, and the NF-κB and MMP-9 protein levels were further decreased. Similar results were observed after PDTC (NF-κB inhibitor) co-treatment. Conversely, SC79, an Akt activator, could partially reverse the anti-metastatic effects of Tet, accompanied by the restoration of NF-κB and MMP-9 protein levels. In conclusion, the current results indicated that Tet inhibited migration and invasion of RCC partially by regulating Akt/NF-κB/MMP-9 signaling pathway, suggesting that Tet may be a potential therapeutic candidate against metastatic RCC.

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“…Nonetheless, KISS1R activation through kisspeptins may lead to suppression of ERK activation, which culminates with a reduction in matrix metalloproteinase 9 (MMP-9) expression and ultimately inhibition of tumor metastasis. 24,27 Regarding the aforementioned points, analysis of DNA methylation in EDNRB and KISS1 genes seems to be important in developing new diagnostic biomarkers; therefore, this study aims at quantitatively analyzing the methylation status of these genes in sporadic CRC patients using Methylation-Sensitive High Resolution Melting (MS-HRM) assay. Furthermore, the correlation of clinicopathological parameters and aberrant methylation of both genes will be detected.…”

Section: Introductionmentioning

confidence: 99%

Aberrant methylated EDNRB can act as a potential diagnostic biomarker in sporadic colorectal cancer while KISS1 is controversial

et al. 2017

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Cancers are among the most serious threats of human health worldwide. Survival and mortality rates of colorectal cancer (CRC) strongly depend on the early diagnosis. The aberrant methylation pattern of genes as a diagnostic biomarker can serve as a practical option for timely detection and contribute subsequently to the enhancement of survival rate in CRC patients, since methylation changes are not only frequent but also can occur in initial tumorogenesis stages. It has been indicated that EDNRB and KISS1 genes are hypermethylated through progression and development of CRC. In current study, after extraction of genomic DNA from 45 paired tumor and adjacent noncancerous tissue samples and treatment with bisulfite conversion, the methylation status of EDNRB and KISS1 CpG rich regions were assessed quantitatively using MS-HRM assay to determine practicability of these aberrant methylations for diagnosis of sporadic CRC and its discrimination from corresponding normal tissues. The results showed that the methylation distribution differences, comparing tumor tissues with their adjacent non-cancerous tissues, were statistically significant in all selected locations within EDNRB gene promoter (P < 0.001); they had also some correlations with tumor stage and grade. Nonetheless, methylation distribution in KISS1 gene CpG rich region revealed no statistically significant differences between CRC and adjacent noncancerous tissues (P D 0.060). Overall, it can be concluded that aberrant methylated EDNRB can be a promising potential diagnostic biomarker for CRC, while KISS1 is controversial and needs to be more investigated.

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Overexpression of KiSS-1 reduces colorectal cancer cell invasion by downregulating MMP-9 via blocking PI3K/Akt/NF-κB signal pathway

Cited by 51 publications

References 23 publications

TCF21 functions as a tumor suppressor in colorectal cancer through inactivation of PI3K/AKT signaling

TCF21 functions as a tumor suppressor in colorectal cancer through inactivation of PI3K/AKT signaling

Tetrandrine inhibits migration and invasion of human renal cell carcinoma by regulating Akt/NF-κB/MMP-9 signaling

Aberrant methylated EDNRB can act as a potential diagnostic biomarker in sporadic colorectal cancer while KISS1 is controversial

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