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Actin-like 6A predicts poor prognosis of hepatocellular carcinoma and promotes metastasis and epithelial-mesenchymal transition.

Xiao S, Chang RM, Yang MY, Lei X, Liu X, Gao WB, Xiao JL, Yang LY - Hepatology (2016)

Bottom Line: Opposite results are observed when ACTL6A is knocked down.ACTL6A knockdown has the equal blockage effect as the Notch signaling inhibitor, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butylester, in HCC cells.Further studies indicate that ACTL6A might manipulate SRY (sex determining region Y)-box 2 (SOX2) expression and then activate Notch1 signaling.

View Article: PubMed Central - PubMed

Affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.

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ACTL6A promotes invasion, metastasis, and EMT through Notch signaling. (A) Migration and invasion assays for PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A and their control cells with/without DAPT treatment. (B) IF assay of E‐cadherin and vimentin expressions in PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A, and their control cells with/without DAPT treatment. (C) EMT‐related protein expression in PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A, and their control cells with/without DAPT treatment. (D) Representative IHC images of ACTL6A, NICD1, vimentin, E‐cadherin, and snail expression in liver orthotopic transplantation tumor generated from PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A and their control cells; magnification: 400×.
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hep28417-fig-0005: ACTL6A promotes invasion, metastasis, and EMT through Notch signaling. (A) Migration and invasion assays for PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A and their control cells with/without DAPT treatment. (B) IF assay of E‐cadherin and vimentin expressions in PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A, and their control cells with/without DAPT treatment. (C) EMT‐related protein expression in PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A, and their control cells with/without DAPT treatment. (D) Representative IHC images of ACTL6A, NICD1, vimentin, E‐cadherin, and snail expression in liver orthotopic transplantation tumor generated from PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A and their control cells; magnification: 400×.

Mentions: To further study the role of ACTL6A and Notch signaling in invasion, metastasis, and EMT of HCC, we first measured the invasive capacity of ACTL6A‐interfered HCC cells with or without DAPT treatment. Wound‐healing and transwell assays showed that DAPT treatment obviously decreased the migration and invasion capacity of ACTL6A high‐expression cells, but had none or less effect for PLC/PRF5 and Hep3B‐shACTL6A cells in which ACTL6A expression and Notch1 activity was low (Fig. 5A and Supporting Fig. 8A,B). IF analysis revealed that DAPT treatment increased E‐cadherin expression, and decreased vimentin expression in PLC/PRF5‐ACTL6A and Hep3B cells, but they were not significantly altered for PLC/PRF5 and Hep3B‐shACTL6A cells (Fig. 5B). Anchorage‐independent growth assay also indicated that DAPT treatment decreased the clonogenic capacity of cells with a high ACTL6A level (Supporting Fig. 8C). Western blotting analysis indicated that DAPT treatment increased epithelial marker (E‐cadherin) expression and decreased mesenchymal marker (vimentin and snail) expression in cells with a high level of ACTL6A, and ACTL6A expression had no considerable change (Fig. 5C). Moreover, IHC analysis of liver orthotopic transplantation tumor showed that NICD1, vimentin, and snail expression levels were high in tumors with a high level of ACTL6A and were low in tumors with poor expression of ACTL6A. Correspondingly, E‐cadherin expression was the opposite (Fig. 5D). Taken together, we concluded that ACTL6A promoted invasion, metastasis, and EMT through Notch signaling in HCC.


Actin-like 6A predicts poor prognosis of hepatocellular carcinoma and promotes metastasis and epithelial-mesenchymal transition.

Xiao S, Chang RM, Yang MY, Lei X, Liu X, Gao WB, Xiao JL, Yang LY - Hepatology (2016)

ACTL6A promotes invasion, metastasis, and EMT through Notch signaling. (A) Migration and invasion assays for PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A and their control cells with/without DAPT treatment. (B) IF assay of E‐cadherin and vimentin expressions in PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A, and their control cells with/without DAPT treatment. (C) EMT‐related protein expression in PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A, and their control cells with/without DAPT treatment. (D) Representative IHC images of ACTL6A, NICD1, vimentin, E‐cadherin, and snail expression in liver orthotopic transplantation tumor generated from PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A and their control cells; magnification: 400×.
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hep28417-fig-0005: ACTL6A promotes invasion, metastasis, and EMT through Notch signaling. (A) Migration and invasion assays for PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A and their control cells with/without DAPT treatment. (B) IF assay of E‐cadherin and vimentin expressions in PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A, and their control cells with/without DAPT treatment. (C) EMT‐related protein expression in PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A, and their control cells with/without DAPT treatment. (D) Representative IHC images of ACTL6A, NICD1, vimentin, E‐cadherin, and snail expression in liver orthotopic transplantation tumor generated from PLC/PRF5‐ACTL6A, Hep3B‐shACTL6A and their control cells; magnification: 400×.
Mentions: To further study the role of ACTL6A and Notch signaling in invasion, metastasis, and EMT of HCC, we first measured the invasive capacity of ACTL6A‐interfered HCC cells with or without DAPT treatment. Wound‐healing and transwell assays showed that DAPT treatment obviously decreased the migration and invasion capacity of ACTL6A high‐expression cells, but had none or less effect for PLC/PRF5 and Hep3B‐shACTL6A cells in which ACTL6A expression and Notch1 activity was low (Fig. 5A and Supporting Fig. 8A,B). IF analysis revealed that DAPT treatment increased E‐cadherin expression, and decreased vimentin expression in PLC/PRF5‐ACTL6A and Hep3B cells, but they were not significantly altered for PLC/PRF5 and Hep3B‐shACTL6A cells (Fig. 5B). Anchorage‐independent growth assay also indicated that DAPT treatment decreased the clonogenic capacity of cells with a high ACTL6A level (Supporting Fig. 8C). Western blotting analysis indicated that DAPT treatment increased epithelial marker (E‐cadherin) expression and decreased mesenchymal marker (vimentin and snail) expression in cells with a high level of ACTL6A, and ACTL6A expression had no considerable change (Fig. 5C). Moreover, IHC analysis of liver orthotopic transplantation tumor showed that NICD1, vimentin, and snail expression levels were high in tumors with a high level of ACTL6A and were low in tumors with poor expression of ACTL6A. Correspondingly, E‐cadherin expression was the opposite (Fig. 5D). Taken together, we concluded that ACTL6A promoted invasion, metastasis, and EMT through Notch signaling in HCC.

Bottom Line: Opposite results are observed when ACTL6A is knocked down.ACTL6A knockdown has the equal blockage effect as the Notch signaling inhibitor, N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butylester, in HCC cells.Further studies indicate that ACTL6A might manipulate SRY (sex determining region Y)-box 2 (SOX2) expression and then activate Notch1 signaling.

View Article: PubMed Central - PubMed

Affiliation: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, China.

Show MeSH
Related in: MedlinePlus