Rab11-FIP2 promotes colorectal cancer migration and invasion by regulating PI3K/AKT/MMP7 signaling pathway

Xu, Chunyan; Wang, Jianzhang; Xia, Xuanping; Pan, Chen‐Wei; Shao, Xiao-xiao; Xia, Shenglong; Yang, Shou‐Xing; Zheng, Bo

doi:10.1016/j.bbrc.2016.01.031

Cited by 40 publications

(33 citation statements)

References 33 publications

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“…Alternatively, CCAR2 could interact with some transcriptional regulators and modulate their activity differently in cancer and normal cells. Accordingly, the expression of genes implicated in the induction of AKT function, such as MSR1 and RAB11-FIP1, 22, 23 has been found deregulated in BJ-hTERT cells and, on the contrary, genes involved in AKT repression are specifically altered in U2OS cells. Another possibility is that CCAR2 loss, which is known to induce metabolic defects, 24 could be more detrimental in cancer than in normal cells because of the Warburg effect and because of normal cells ability to activate AKT also in the absence of CCAR2.…”

Section: Discussionmentioning

confidence: 99%

A novel crosstalk between CCAR2 and AKT pathway in the regulation of cancer cell proliferation

et al. 2016

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Human CCAR2 has recently emerged as having a pivotal role in the DNA damage response, promoting apoptosis and repair of heterochromatic DNA breaks. However, less is known about the function of CCAR2 in tumor formation and cancer progression. Here, we demonstrate, for the first time, that CCAR2 loss inhibits the proliferation of cancer cells, but preserves the growth of normal cells. Investigating the mechanisms responsible for this differential effect, we found that CCAR2 depletion specifically impairs the activation of AKT pathway in cancer cells, but not in normal cells, by reducing AKT phosphorylation on Ser473. This effect is achieved through the transcriptional upregulation of TRB3 gene and accumulation of TRB3 protein, which then binds to and inhibits the phosphorylation and activation of AKT. The defective activation of AKT finally results in reduced GSK3β phosphorylation, prevention of G1/S transition and inhibition of cancer cell growth. These results establish an important role for CCAR2 in cancer cells proliferation and could shed new light on novel therapeutic strategies against cancer, devoid of detrimental side effects.

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Section: Discussionmentioning

confidence: 99%

A novel crosstalk between CCAR2 and AKT pathway in the regulation of cancer cell proliferation

et al. 2016

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“…Akt and ERK signalling pathways play important roles in CRC progression. It has been proved that activated PI3K/Akt signalling pathway promotes proliferation, migration and invasion and attenuates apoptosis of CRC cells . ERK is an important factor for regulating proliferation, apoptosis, migration and invasion through various signalling in CRC cells .…”

Section: Discussionmentioning

confidence: 99%

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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“…Additionally, a study of prostate cancer with neuroendocrine differentiation demonstrated that MMP7 leads to increased endothelial cell coverage and enlarged vessel size, resulting in increased invasion of neighboring tissue . It has been reported that upregulation of MMP7 expression is caused by activation of the PI3K/Akt pathway and is required for the migration and invasion of colorectal cancer cells . A study of gastric cancer indicated that the EGF‐induced overexpression of MMP7 depends on the PI3K signaling cascade …”

Section: Discussionmentioning

confidence: 99%

“…43 It has been reported that upregulation of MMP7 expression is caused by activation of the PI3K/Akt pathway and is required for the migration and invasion of colorectal cancer cells. 44 A study of gastric cancer indicated that the EGF-induced overexpression of MMP7 depends on the PI3K signaling cascade. 45 Moreover, a previous study revealed that MMP7 cleaves CLEC3A bound to the cell surfaces of various cancer cell lines, including colon, breast, and lung cancer cells.…”

Section: Discussionmentioning

confidence: 99%

CLEC3A, MMP7, and LCN2 as novel markers for predicting recurrence in resected G1 and G2 pancreatic neuroendocrine tumors

et al. 2019

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Although the postoperative recurrence rate for pancreatic neuroendocrine tumors (PNETs) is reported to be 13.5%‐30%, the paucity of valuable biomarkers to predict recurrence poses a problem for the early detection of relapse. Hence, this study aimed to identify new biomarkers to predict the recurrence of PNETs. We performed RNA sequencing (RNA‐Seq) on RNA isolated from frozen primary tumors sampled from all localized G1/G2 PNETs resected curatively from 1998 to 2015 in our institution. We calculated differentially expressed genes (DEGs) in tumor with and without recurrence (≥3 years) for the propensity‐matched cohort. Gene ontology analysis for the identified DEGs was also performed. Furthermore, we evaluated the expression levels of candidate genes as recurrence predictors via immunostaining. Comparison of transcriptional levels in tumors with and without recurrence identified 166 DEGs. Up‐ and downregulated genes with high significance in these tumors were mainly related to extracellular organization and cell adhesion, respectively. We observed the top three upregulated genes, C‐type lectin domain family 3 member A (CLEC3A), matrix metalloproteinase‐7 (MMP7), and lipocalin2 (LCN2) immunohistochemically and compared their levels in recurrent and nonrecurrent tumors. Significantly higher recurrence rate was shown in patients with positive expression of CLEC3A ( P = 0.028), MMP7 ( P = 0.003), and LCN2 ( P = 0.040) than that with negative expression. We identified CLEC3A, MMP7, and LCN2 known to be associated with the phosphatidylinositol‐3‐kinase/Akt pathway, as potential novel markers to predict the postoperative recurrence of PNETs.

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Rab11-FIP2 promotes colorectal cancer migration and invasion by regulating PI3K/AKT/MMP7 signaling pathway

Cited by 40 publications

References 33 publications

A novel crosstalk between CCAR2 and AKT pathway in the regulation of cancer cell proliferation

A novel crosstalk between CCAR2 and AKT pathway in the regulation of cancer cell proliferation

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

CLEC3A, MMP7, and LCN2 as novel markers for predicting recurrence in resected G1 and G2 pancreatic neuroendocrine tumors

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