title: HOXC6 promotes gastric cancer cell invasion by upregulating the expression of MMP9.
abstract: Previous studies have demonstrated that the homoebox C6 (HOXC6) gene is highly expressed in gastric cancer tissues and is associated with the depth of tumor invasion, and is associated with poor prognosis of gastric cancer patients expressing HOXC6. The present study investigated the effect and underlying mechanism of HOXC6 on the proliferation and metastasis of gastric cancer cells in vitro. Reverse transcription‑quantitative polymerase chain (PCR) reaction was used to investigate the expression levels of HOXC6 in different gastric cancer cell lines and the effect of different levels of expression on the proliferation of gastric cancer cells was determined by cell growth curve and plate colony formation. The effect of HOXC6 on the anchorage‑independent proliferation of gastric cancer cells was determined by soft agar colony formation assay while the Transwell invasion assay was used to investigate the effect of different levels of HOXC6 expression on the invasive and metastatic abilities of gastric cancer cells. Semi‑quantitative PCR was used to detect the effect of different levels of HOXC6 expression on the expression of matrix metalloproteinase (MMP)2 and MMP9 in gastric cancer cells. Immunoblotting was used to assess MMP9 signaling in the gastric cancer cells. The HOXC6 gene is highly expressed in the majority of the gastric cancer cell lines. Overexpression of HOXC6 promoted gastric cancer cell proliferation and colony formation ability while HOXC6 downregulation inhibited cell proliferation and clone forming ability. HOXC6 overexpression also enhanced the soft agar colony formation ability of gastric cancer cells while HOXC6 downregulation decreased the colony formation ability. Upregulated HOXC6 increased the migration and invasion abilities of gastric cancer cells while interfering with HOXC6 expression inhibited the migration and invasion of the gastric cancer cells. The expression of MMP9 was enhanced with an upregulation of HOXC6 expression while HOXC6 downregulation lowered MMP9 gene expression levels. Increased expression of HOXC6 in gastric cancer cell lines significantly activated extracellular signal‑regulated kinase signaling and upregulated MMP9. The HOXC6 gene promotes the proliferation of gastric cancer cells while upregulation of MMP9 promotes migration and invasion of gastric cancer cells.
authors: Department of Medical Oncology, Gongli Hospital, Shanghai 200135, P.R. China.
authors: Shi-Wei
authors: SW
authors: Chen
authors: Department of Medical Oncology, Gongli Hospital, Shanghai 200135, P.R. China.
authors: Qing
authors: Q
authors: Zhang
authors: Department of Medical Oncology, Gongli Hospital, Shanghai 200135, P.R. China.
authors: Zhi-Feng
authors: ZF
authors: Xu
authors: Department of Medical Oncology, Gongli Hospital, Shanghai 200135, P.R. China.
authors: Hai-Ping
authors: HP
authors: Wang
authors: Department of Medical Oncology, Gongli Hospital, Shanghai 200135, P.R. China.
authors: Yi
authors: Y
authors: Shi
authors: Department of Medical Oncology, Gongli Hospital, Shanghai 200135, P.R. China.
authors: Feng
authors: F
authors: Xu
authors: Department of Clinical Medicine, School of Medicine, Shandong University, Jinan, Shandong 250012, P.R. China.
authors: Wen-Jian
authors: WJ
authors: Zhang
authors: Department of Pathology, Shanghai Ninth People's Hospital Affiliated Shanghai Jiaotong University School of Medicine, Shanghai 200011, P.R. China.
authors: Ping
authors: P
authors: Wang
authors: Department of Medical Oncology, Gongli Hospital, Shanghai 200135, P.R. China.
authors: Yong
authors: Y
authors: Li
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D013270:Stomach / Q000473:pathology*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D015854:Up-Regulation
chemical_list: C094289:HOXC6 protein, human; D018398:Homeodomain Proteins; D020780:Matrix Metalloproteinase 9