MACC-1 Promotes Endothelium-Dependent Angiogenesis in Gastric Cancer by Activating TWIST1/VEGF-A Signal Pathway.
Endothelium-dependent angiogenesis is thought to be a crucial step in cancer progression. We previously reported that metastasis-associated in colon cancer-1 (MACC1) contributed to the vasculogenic mimicry in gastric cancer (GC), but it remains unknown whether MACC1 promotes endothelium-dependent angiogenesis of GC and whether TWIST1 is involved in this process. In the present study, we detected MACC1 expression and microvessel density (MVD) by immunohistochemistry in 159 patients with stage I-III GC, and investigated the role of TWIST1 and vascular endothelial growth factor A (VEGF-A) in MACC1-induced endothelium-dependent angiogenesis using nude mice with GC xenografts, and human umbilical vein endothelial cells (HUVECs) that were co-cultured with conditioned media from overexpression and interference MACC1 GC cells. We found that MACC1 expression was positively correlated with an increased MVD and tumor recurrence in GC patients. In GC xenograft models, MACC1 elevated MVD and upregulated the expression of VEGF-A as well as accelerated tumor growth. In addition, MACC1 obviously increased the expression of TWIST1 and induced tube-like formation of HUVECs, whereas attenuation of TWIST1 suppressed the protein expression of VEGF-A and repealed the effect of MACC1 on tube formation. Our findings shed light on the function of MACC1 in endothelium-dependent angiogenesis of GC and suggest potential prognostic and therapeutic value.
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Lin
L
Wang
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Rui
R
Zhou
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Yang
Y
Zhao
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Shaoting
S
Dong
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Jingwen
J
Zhang
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Yuhao
Y
Luo
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Na
N
Huang
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Min
M
Shi
Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Jianping
J
Bin
Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Yulin
Y
Liao
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Wangjun
W
Liao
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009364:Neoplasm Recurrence, Local / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; C544162:MACC1 protein, human; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A