title: TGF-β1 induces PGP9.5 expression in CAFs to promote the growth of colorectal cancer cells.
abstract: Numerous studies indicate that the interaction between cancer-associated fibroblasts (CAFs) and tumors is manifested in the entire process of colorectal cancer (CRC) cell development, in which TGF-β1 plays a key role and has a significant effect on promoting the activation of CAFs. However, there are few studies on the mechanisms involved in the activation of CAFs by TGF-β1 to produce an influence on tumor cells. TGF-β1 was added to CAFs for further culture, and the expression of α-SMA was significantly enhanced as shown by immunofluorescence assay. Western blot analysis was performed, and the results showed that TGF-β1 promoted expression of PGP9.5 in a time-dependent manner. After siRNA was used to inhibit the expression of Smad2 or Smad3, the TGF-β1-induced PGP9.5 expression in CAFs was obviously suppressed. In addition, TGF-β1 was also found to promote the expression of PGP9.5 through the ERK1/2 and PI3K pathways. CAFs were cultured on the upper layer of a Transwell plate and TGF-β1 was added. Simultaneously, CRC cells were cultured on the lower layer. The biological behaviors of the cancer cells were detected. According to the results, TGF-β1 promoted the proliferation and invasion of CRC cells and inhibited their apoptosis while activating CAFs. This effect was achieved by induction of the expression of PGP9.5. However, when PGP9.5 was inhibited, the impact of TGF-β1 on tumor cells after activation of CAFs was not fully blocked. Therefore, TGF-β1 can promote PGP9.5 expression in CAFs to facilitate the growth of cancer cells. This finding aids in the identification of new targets for treating CRC.
authors.affiliation: Medical Department, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wen
authors.affiliation: Department of Anorectal Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Ge
authors.initials: G
authors.lastname: Liu
authors.affiliation: Emergency Department, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Jin
authors.affiliation: Gastrointestinal Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Hu
mesh_terms: D002450:Cell Communication / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000473:pathology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology / Q000502:physiology*; D059016:Tumor Microenvironment / Q000187:drug effects / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase