SMC1A recruits tumor-associated-fibroblasts (TAFs) and promotes colorectal cancer metastasis.
Tumor-associated-fibroblasts (TAFs) are the most important host cells in the stroma and take part in extracellular matrix construction and cancer colony development. During cancer colonization, seed cells from primary tumor can reconstruct the microenvironment by recruiting circulating cancer cells and TAFs to the metastasis site. Previous studies have established that SMC1A, a subunit of cohesin, is an important trigger signal for liver metastasis in colorectal cancer. We investigated the particular effects as well as the underlying mechanism of SMC1A on TAFs recruitment during liver metastasis of colorectal cancer. Here, We found that: first, the high expression of SMC1A in colorectal cancer cells promotes the invasiveness and the viability of these cells by recruiting circulating TAFs, facilitating early tumor construction and tumorigenesis; second, different expression levels of SMC1A influenced the reformation of fibroblasts, which assisted tumorigenesis, and third, expression of SMC1A stimulated the secretion of the inflammatory mediators of TNF-α and IL-1β, and up-regulated the transcriptional expression of MMP2 and VEGF-β, both of which were involved in the tumor-related gene pathway.
Department of Surgical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang 310009, China.
Pengyang
P
Zhou
Department of Surgical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang 310009, China.
Nan
N
Xiao
Department of Surgical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang 310009, China.
Jian
J
Wang
Department of Surgical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang 310009, China.
Zhanhuai
Z
Wang
Department of Surgical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang 310009, China.
Shuchun
S
Zheng
Department of Surgical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang 310009, China.
Siyang
S
Shan
Department of Colorectal and Anal Surgery, The Jinhua Hospital of Zhejiang University, Zhejiang, China.
Jianping
J
Wang
Department of Colorectal and Anal Surgery, The Jinhua Hospital of Zhejiang University, Zhejiang, China.
Jinlin
J
Du
Department of Surgical Oncology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang 310009, China. Electronic address: sypzju@zju.edu.cn.
Jianwei
J
Wang
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D000818:Animals; D000072645:Cancer-Associated Fibroblasts / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D002633:Chemotaxis; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D042561:Vascular Endothelial Growth Factor B / Q000235:genetics / Q000378:metabolism; D000098550:Structural Maintenance of Chromosome Protein 1
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C508585:IL1B protein, human; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; C467485:VEGFB protein, human; D042561:Vascular Endothelial Growth Factor B; D000098550:Structural Maintenance of Chromosome Protein 1; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
Colorectal liver metastasis; Recruitment; SMC1A; Tumor-associated-fibroblasts; Tumorigenesis