Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways

Zhao, Jingkun; Ou, Baochi; Han, Dingpei; Wang, Puxiongzhi; Zong, Yaping; Zhu, Congcong; Liu, Di; Zheng, Min; Sun, Jing Ping; Feng, Hao; Liu, Aiguo

doi:10.1186/s12943-017-0629-4

Cited by 218 publications

(191 citation statements)

References 39 publications

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“…[33][34][35] ERK is an important factor for regulating proliferation, apoptosis, migration and invasion through various signalling in CRC cells. [36][37][38][39] Our findings demonstrated that overexpression of SPNS2 increased Akt and ERK phosphorylation and SPNS2-induced malignant behaviours were abolished by Akt or ERK inhibitor, suggesting that SPNS2 may regulate the malignancy of CRC cells by activating Akt and ERK signalling.…”

Section: Discussionmentioning

confidence: 54%

SPNS2 promotes the malignancy of colorectal cancer cells via regulating Akt and ERK pathway

Jiang

Wang

et al. 2019

Clin Exp Pharma Physio

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Colorectal cancer (CRC) is a prevalent malignant tumour that causes considerable cancer‐related deaths globally. The sphingolipid transporter 2 (SPNS2), a sphingosine‐1‐phosphate (S1P) transporter, modulates multiple biological events including malignancy of cancer cells. In this study, the effects of SPNS2 on CRC progression were studied. We found that SPNS2 expression was significantly upregulated in CRC tissues compared to that in adjacent non‐tumour tissues. To assess the role of SPNS2 in CRC cells, we performed loss‐ and gain‐of‐function experiments in SW480 and HCT116 cells, respectively. The results demonstrated that SPNS2 promoted proliferation, migration and invasion, and inhibited apoptosis in CRC cells. Additionally, SPNS2 enhanced the release of intracellular S1P, and increased S1P receptor 1 (S1PR1) and S1PR3 expression. Moreover, SPNS2 activated the Akt and ERK pathways, and the biological behaviours of SPNS2 were attenuated by Akt or ERK inhibitor in HCT116 cells. In conclusion, our results demonstrated that SPNS2 promoted proliferation, migration and invasion, and inhibited apoptosis by regulating S1P/S1PR1/3 axis and activating Akt and ERK pathway in CRC cells.

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Section: Discussionmentioning

confidence: 54%

SPNS2 promotes the malignancy of colorectal cancer cells via regulating Akt and ERK pathway

Jiang

Wang

et al. 2019

Clin Exp Pharma Physio

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“…As a confirmation, immunofluorescent staining and IHC showed increased CXCL5 expression in CAFs. In addition, it was demonstrated that nonsmall cell lung cancer, melanoma and CRC tumor cell lines also highly expressed CXCL5 which mold tumor microenvironment . Therefore, it seemed that CXCL5 was with diverse origins.…”

Section: Discussionmentioning

confidence: 73%

Cancer‐associated fibroblasts promote PD‐L1 expression in mice cancer cells via secreting CXCL5

Zhou

Zhang

et al. 2019

Intl Journal of Cancer

152

131

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Cancer‐associated fibroblasts (CAFs) play a key role in orchestrating the tumor malignant biological properties within tumor microenvironment and evidences demonstrate that CAFs are a critical regulator of tumoral immunosuppression of the T cell response. However, the functions and regulation of CAFs in the expression of programmed death‐ligand 1 (PD‐L1) in melanoma and colorectal carcinoma (CRC) are not completely understood. Herein, by scrutinizing the expression of α‐SMA and PD‐L1 in melanoma and CRC tissues, we found that CAFs was positive correlated with PD‐L1 expression. Further analyses showed that CAFs promoted PD‐L1 expression in mice tumor cells. By detecting a majority of cytokines expression in normal mice fibroblasts and CAFs, we determined that CXCL5 was abnormal high expression in CAFs and the immunohistochemistry and in situ hybridization confirmed that were CAFs which were expressing CXCL5. In addition, CXCL5 promoted PD‐L1 expression in B16, CT26, A375 and HCT116. The silencing of CXCR2, the receptor of CXCL5, inhibited the PD‐L1 expression induced by CAFs in turn. Functionally, CXCL5 derived by CAFs promoted PD‐L1 expression in mice tumor cells through activating PI3K/AKT signaling. LY294002, the inhibitor of PI3K, confirmed that CXCL5 forested an immunosuppression microenvironment by promoting PD‐L1 expression via PI3K/AKT signaling. Meanwhile, the B16/CT26 xenograft tumor models were used and both CXCR2 and p‐AKT were found to be positively correlated with PD‐L1 in the xenograft tumor tissues. The immunosuppressive action of CAFs on tumor cells is probably reflective of them being a potential therapeutic biomarker for melanoma and CRC.

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“…Our studies suggested that TIMM50 also promoted tumor proliferation and invasion in NSCLC cells via upregulating Cyclin D1 and Snail and downregulating E‐cadherin. During tumor progression, multiple signaling pathways, such as ERK, AKT, P38, and FAK, were involved in modulating the expression of Cyclin D1, Snail, and E‐cadherin . Using Western blotting analysis, we found that overexpression of TIMM50 was capable of upregulating the levels of phosphorylated ERK and P90RSK.…”

Section: Discussionmentioning

confidence: 94%

TIMM50 promotes tumor progression via ERK signaling and predicts poor prognosis of non‐small cell lung cancer patients

Zhang

Han

Zhou

et al. 2019

Molecular Carcinogenesis

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TIMM50 (Translocase of the inner mitochondrial membrane 50), also called TIM50, plays an essential role in mitochondrial membrane transportation. The existing literature suggests that TIMM50 may perform as an oncogenetic protein in breast cancer. However, the molecular mechanism, especially in human non‐small cell lung cancer (NSCLC), is uncertain to date. In the present study, using immunohistochemistry, we found that TIMM50 expression significantly correlated with larger tumor size (P = 0.049), advanced TNM stage (P = 0.001), positive regional lymph node metastasis (P = 0.007), and poor overall survival (P = 0.001). Proliferation and invasion assay showed that TIMM50 dramatically promoted the ability of proliferation and invasion of NSCLC cells. Subsequent Western blotting results revealed that TIMM50 enhanced the expression of Cyclin D1 and Snail, and inhibited the expression of E‐cadherin. Moreover, TIMM50 facilitated the expression of phosphorylated ERK and P90RSK. Incorporation of ERK inhibitor counteracted the upregulating expression of CyclinD1, and Snail, and downregulating expression of E‐cadherin expression induced by TIMM50 overexpression. In conclusion, our data indicated that TIMM50 facilitated tumor proliferation and invasion of NSCLC through enhancing phosphorylation of its downstream ERK/P90RSK signaling pathway. We speculated that TIMM50 might be a useful prognosis marker of NSCLC patients.

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Tumor-derived CXCL5 promotes human colorectal cancer metastasis through activation of the ERK/Elk-1/Snail and AKT/GSK3β/β-catenin pathways

Cited by 218 publications

References 39 publications

SPNS2 promotes the malignancy of colorectal cancer cells via regulating Akt and ERK pathway

SPNS2 promotes the malignancy of colorectal cancer cells via regulating Akt and ERK pathway

Cancer‐associated fibroblasts promote PD‐L1 expression in mice cancer cells via secreting CXCL5

TIMM50 promotes tumor progression via ERK signaling and predicts poor prognosis of non‐small cell lung cancer patients

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