CEACAM6 promotes tumor angiogenesis and vasculogenic mimicry in gastric cancer via FAK signaling

Zang, Mingde; Zhang, Yunqiang; Zhang, Baogui; Hu, Lei; Li, Jianfang; Fan, Zhiyuan; Wang, Hexiao; Su, Liping; Zhu, Zhenggang; Li, Chen; Yan, Chao; Gu, Qinxuan; Liu, Bingya; Yan, Min

doi:10.1016/j.bbadis.2015.02.005

Cited by 60 publications

(37 citation statements)

References 28 publications

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“…Tumor progression is not only associated with cancer cell metastasis, but also with tumor angiogenesis (3). There must be angiogenesis tubular formation in tumors with a diameter of ~2 mm (22).…”

Section: Discussionmentioning

confidence: 99%

PBX3 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition

Wang

et al. 2016

Oncology Letters

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The overexpression of pre-leukemia transcription factor 3 (PBX3) in tumors plays an important role in invasion, metastasis and proliferation in a variety of human cancer types. Tumor metastasis and angiogenesis significantly contribute to the progression of cancer and create challenges for cancer therapy. In the present study, reverse transcription-polymerase chain reaction demonstrated that PBX3 was upregulated in gastric cancer (GC) tissues and Transwell assay revealed that the overexpression of PBX3 promoted GC invasion and metastasis in vitro. In addition, a nude mouse xenograft model was established, which demonstrated that PBX3 promoted peritoneal metastases in vivo. Furthermore, the overexpression of PBX3 in GC promoted the tubular formation of human umbilical vein endothelial cells. Western blot analysis revealed that overexpressed PBX3 induced epithelial-mesenchymal transition (EMT) in GC, as measured by increases in the EMT protein markers N-cadherin and vimentin, while E-cadherin expression was reduced in PBX3-overexpressing GC cells. Contrasting results were observed in PBX3-knockdown GC cells. Additionally, the overexpression of PBX3 increased the levels of phosphorylated AKT (Ser473), which is involved in the progression of a variety of human cancers. Gelatin zymography assay demonstrated that the overexpression of PBX3 also elevated matrix metalloproteinase-9 activity in GC, which was closely associated with tumor metastasis and angiogenesis. Based on these findings, it may be concluded that PBX3 enhances invasion and metastasis in GC by promoting EMT, possibly via the AKT signaling pathway.

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Section: Discussionmentioning

confidence: 99%

PBX3 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition

Wang

et al. 2016

Oncology Letters

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“…In general, tumor progression is accompanied by rich angiogenesis to satisfy the metabolic requirements [11]. Tumor metastasis is a major contributor to cancer-related death and the process of capillary formation in tumor is a crucial aspect to enable metastasis, especially when tumors diameter approximates 2 mm [12]. The poor outcome of PaC is closely associate with the tendency to spread to surrounding tissues, approximately 50% of PaC patients present with distant metastatic disease [13], which is significantly correlated with the phenomenon of angiogenesis [14, 15].…”

Section: Introductionmentioning

confidence: 99%

“…Many efforts have been made to inhibit the angiogenesis for PaC. However, traditional anti-vascular drug may promote tumor progression by inducing hypoxia which insteadly stimulates angiogenesis, so novel anti-vascular therapy should be applied [12]. To our knowledge, there are various molecular factors involved in vascular growth.…”

Section: Introductionmentioning

confidence: 99%

Periostin promotes tumor angiogenesis in pancreatic cancer via Erk/VEGF signaling

Liu

Gao

et al. 2016

Oncotarget

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Pancreatic cancer (PaC) consists of a bulk of stroma cells which contribute to tumor progression by releasing angiogenic factors. Recent studies have found that periostin (POSTN) is closely associate with the metastatic potential and prognosis of PaC. The purpose of this study is to determine the role of POSTN in tumor angiogenesis and explore the precise mechanisms. In this study, we used lentiviral shRNA and human recombinant POSTN protein (rPOSTN) to negatively and positively regulate POSTN expression in vitro. We found that increased POSTN expression promoted the tubule formation dependent on human umbilical vein endothelial cells (HUVECs). Moreover, knockdown of POSTN in PaC cells reduced tumor growth and VEGF expression in vivo. In accordance with these observations, we found that Erk phosphorylation and its downstream VEGF expression were upregulated achieved in rPOSTN-treated groups, opposing results were obversed in POSTN-slienced group. Meanwhile, Erk inhibitor SCH772984 significantly decreased VEGF expression as well as tubule formation of HUVECs in rPOSTN-treated PaC cells. Taken together, these findings suggest that POSTN promotes tumor angiogenesis via Erk/VEGF signaling in PaC and POSTN may be a new target for cancer anti-vascular treatment.

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“…15,18 It was reported that the inhibition of tumor metastasis could remarkably enhance survival rates of tumor patients. 19 Octreotide (OCT) is a synthetic 8-peptide analog of somatostatin and mainly binds to somatostatin receptors that are overexpressed in a variety of tumors. 20,21 Somatostatin receptors have been recognized as tumor markers and are used for tumor diagnose and treatment.…”

Section: Introductionmentioning

confidence: 99%

Application of multifunctional targeting epirubicin liposomes in the treatment of non-small-cell lung cancer

Song

Xiao

et al. 2017

IJN

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Chemotherapy for aggressive non-small-cell lung cancer (NSCLC) usually results in a poor prognosis due to tumor metastasis, vasculogenic mimicry (VM) channels, limited killing of tumor cells, and severe systemic toxicity. Herein, we developed a kind of multifunctional targeting epirubicin liposomes to enhance antitumor efficacy for NSCLC. In the liposomes, octreotide was modified on liposomal surface for obtaining a receptor-mediated targeting effect, and honokiol was incorporated into the lipid bilayer for inhibiting tumor metastasis and eliminating VM channels. In vitro cellular assays showed that multifunctional targeting epirubicin liposomes not only exhibited the strongest cytotoxic effect on Lewis lung tumor cells but also showed the most efficient inhibition on VM channels. Action mechanism studies showed that multifunctional targeting epirubicin liposomes could downregulate PI3K, MMP-2, MMP-9, VE-Cadherin, and FAK and activate apoptotic enzyme caspase 3. In vivo results exhibited that multifunctional targeting epirubicin liposomes could accumulate selectively in tumor site and display an obvious antitumor efficacy. In addition, no significant toxicity of blood system and major organs was observed at a test dose. Therefore, multifunctional targeting epirubicin liposomes may provide a safe and efficient therapy strategy for NSCLC.

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CEACAM6 promotes tumor angiogenesis and vasculogenic mimicry in gastric cancer via FAK signaling

Cited by 60 publications

References 28 publications

PBX3 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition

PBX3 promotes gastric cancer invasion and metastasis by inducing epithelial-mesenchymal transition

Periostin promotes tumor angiogenesis in pancreatic cancer via Erk/VEGF signaling

Application of multifunctional targeting epirubicin liposomes in the treatment of non-small-cell lung cancer

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