TGFBR1*6A is a potential modifier of migration and invasion in colorectal cancer cells

  • Authors:
    • Rui Zhou
    • Ying Huang
    • Boran Cheng
    • Yulei Wang
    • Bin Xiong
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  • Published online on: January 4, 2018     https://doi.org/10.3892/ol.2018.7725
  • Pages: 3971-3976
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Abstract

Type 1 transforming growth factor β receptor (TGFBR1)*6A, a common hypomorphic variant of TGFBR1, may act as a susceptibility allele in colorectal cancer. However, the contribution of TGFBR1*6A to colorectal cancer development is largely unknown. To test the hypothesis that TGFBR1*6A promotes colorectal cancer invasion and metastasis via Smad‑independent transforming growth factor‑β (TGF‑β) signaling, the effect of TGFBR1*6A on the invasion of colorectal cancer cells was assessed. pCMV5‑TGFBR1*6A‑HA plasmids were transfected into SW48 and DLD‑1 cells by Lipofectamine-mediated DNA transfection. The effect of TGF‑β1 on the proliferation of SW48 and DLD‑1 cells transfected with TGFBR1*6A was determined by MTT assay. The effects of the TGF‑β1 on the invasion of the transfected SW48 and DLD‑1 cells were determined using Matrigel‑coated plates. Transforming migrating chambers were used to determine the effects of TGF‑β1 on the migration of the transfected SW48 and DLD‑1 cells. Western blot analysis was used to determine the expression of phosphorylated (p‑) extracellular‑signal‑regulated kinase (ERK), p‑P38 and p‑SMAD family member 2 in SW48 cells. Using transfected TGFBR1*6A SW48 and DLD‑1 cell lines our group demonstrated that, in comparison with TGFBR1*9A, TGFBR1*6A is capable of switching TGF‑β1 growth‑inhibitory signals into growth‑stimulatory signals which significantly increased the invasion of SW48 and DLD‑1 cells. Functional assays indicated that TGFBR1*6A weakened Smad‑signaling but increased ERK and p38 signaling, which are crucial mediators of cell migration and invasion. From this, it was possible to conclude that TGFBR1*6A enhanced SW48 cell migration and invasion through the mitogen‑activated protein kinase pathway and that it may contribute to colorectal cancer progression in a TGF‑β1/Smad signaling‑independent manner. This suggests that TGFBR1*6A may possess oncogenic properties and that it may affect the migration and invasion of colorectal cancer cells.
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March-2018
Volume 15 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Zhou R, Huang Y, Cheng B, Wang Y and Xiong B: TGFBR1*6A is a potential modifier of migration and invasion in colorectal cancer cells. Oncol Lett 15: 3971-3976, 2018.
APA
Zhou, R., Huang, Y., Cheng, B., Wang, Y., & Xiong, B. (2018). TGFBR1*6A is a potential modifier of migration and invasion in colorectal cancer cells. Oncology Letters, 15, 3971-3976. https://doi.org/10.3892/ol.2018.7725
MLA
Zhou, R., Huang, Y., Cheng, B., Wang, Y., Xiong, B."TGFBR1*6A is a potential modifier of migration and invasion in colorectal cancer cells". Oncology Letters 15.3 (2018): 3971-3976.
Chicago
Zhou, R., Huang, Y., Cheng, B., Wang, Y., Xiong, B."TGFBR1*6A is a potential modifier of migration and invasion in colorectal cancer cells". Oncology Letters 15, no. 3 (2018): 3971-3976. https://doi.org/10.3892/ol.2018.7725