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Modulator of apoptosis 1 (MOAP-1) is a tumor suppressor protein linked to the RASSF1A protein.

Law J, Salla M, Zare A, Wong Y, Luong L, Volodko N, Svystun O, Flood K, Lim J, Sung M, Dyck JR, Tan CT, Su YC, Yu VC, Mackey J, Baksh S - J. Biol. Chem. (2015)

Bottom Line: It is an integral partner to the tumor suppressor protein, Ras association domain family 1A (RASSF1A), and functions to activate the Bcl-2 family pro-apoptotic protein Bax.Although RASSF1A is now considered a bona fide tumor suppressor protein, the role of MOAP-1 as a tumor suppressor protein has yet to be determined.Overexpression of MOAP-1 in several cancer cell lines resulted in reduced tumorigenesis and up-regulation of genes involved in cancer regulatory pathways that include apoptosis (p53, Fas, and MST1), DNA damage control (poly(ADP)-ribose polymerase and ataxia telangiectasia mutated), those within the cell metabolism (IR-α, IR-β, and AMP-activated protein kinase), and a stabilizing effect on microtubules.

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Affiliation: From the Departments of Biochemistry and.

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MOAP-1 can inhibit tumor formation driven by HCT116 colon cancer cells in vivo. HCT116 colon cancer cells with overexpressed proteins (A and B) or with shRNA to MOAP-1 (C) were generated by transient transfection with the indicated expression vectors. Cells were prepared and injected into nude mice as in Fig. 9. For HCT116 cells, the p value between vector and HA-RASSF1A and vector and Myc-MOAP-1 was 0.0026 and 0.0043, respectively; n = 10–16 for all. B, middle, expression of the indicated constructs are shown as well as mouse and tumor images, B, far right, representative tumors at day 35 of tumor growth. A, tumor images were captured using a multispectral FX instrument from Carestream to support the use of stable expression of GFP constructs for this assay. MOAP-1 shRNA in C results in >70% loss of MOAP-1 expression as presented.
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Figure 8: MOAP-1 can inhibit tumor formation driven by HCT116 colon cancer cells in vivo. HCT116 colon cancer cells with overexpressed proteins (A and B) or with shRNA to MOAP-1 (C) were generated by transient transfection with the indicated expression vectors. Cells were prepared and injected into nude mice as in Fig. 9. For HCT116 cells, the p value between vector and HA-RASSF1A and vector and Myc-MOAP-1 was 0.0026 and 0.0043, respectively; n = 10–16 for all. B, middle, expression of the indicated constructs are shown as well as mouse and tumor images, B, far right, representative tumors at day 35 of tumor growth. A, tumor images were captured using a multispectral FX instrument from Carestream to support the use of stable expression of GFP constructs for this assay. MOAP-1 shRNA in C results in >70% loss of MOAP-1 expression as presented.

Mentions: To directly validate the tumor suppressor function of MOAP-1 in vivo, xenograft tumor assays were performed in athymic nude mice lacking a functioning immune system (25). To carry out these assays, we selected cancer cell lines with reduced or absent MOAP-1 expression (DAOY medulloblastoma cells, SKOV3 and H1299) or with a detectable amount of MOAP-1 (HCT116 cells). Myc-MOAP-1 was transiently expressed in DAOY medulloblastoma cells, SKOV3 (stable expression, ovarian cancer) (Fig. 7, A and B), or H1299 (stable expression, lung cancer, Fig. 7, C and D) and transiently in HCT116 colon cancer cells (Fig. 8, A and B). Following subcutaneous injection of these cells into the left and right flanks of athymic mice, a significant difference in the growth of tumors containing overexpressed Myc-MOAP-1 emerged for all cell lines tested when compared with tumors containing a control vector. This suggested a role for MOAP-1 in growth suppression. Interestingly, the loss of the function of the BH3 domain of MOAP-1 (either as a deletion or mutation) resulted in the inability to suppress tumor formation to suggest a significant dependence of MOAP-1 on its pro-apoptotic function to carry out tumor suppression (Fig. 7, C and D). Complementary to our overexpressed cells, shRNA knockdown of MOAP-1 resulted in a significant increase in tumor formation following subcutaneous injection of HCT116 cells containing shRNA to MOAP-1 (Fig. 8C). Not surprisingly, tumor formation was additionally reduced in the presence of HA-RASSF1A (for DAOY and H1299 cells, Fig. 7, B and C) suggesting a requirement for the RASSF1A/MOAP-1 apoptotic pathway in inhibiting tumor formation in these cell lines.


Modulator of apoptosis 1 (MOAP-1) is a tumor suppressor protein linked to the RASSF1A protein.

Law J, Salla M, Zare A, Wong Y, Luong L, Volodko N, Svystun O, Flood K, Lim J, Sung M, Dyck JR, Tan CT, Su YC, Yu VC, Mackey J, Baksh S - J. Biol. Chem. (2015)

MOAP-1 can inhibit tumor formation driven by HCT116 colon cancer cells in vivo. HCT116 colon cancer cells with overexpressed proteins (A and B) or with shRNA to MOAP-1 (C) were generated by transient transfection with the indicated expression vectors. Cells were prepared and injected into nude mice as in Fig. 9. For HCT116 cells, the p value between vector and HA-RASSF1A and vector and Myc-MOAP-1 was 0.0026 and 0.0043, respectively; n = 10–16 for all. B, middle, expression of the indicated constructs are shown as well as mouse and tumor images, B, far right, representative tumors at day 35 of tumor growth. A, tumor images were captured using a multispectral FX instrument from Carestream to support the use of stable expression of GFP constructs for this assay. MOAP-1 shRNA in C results in >70% loss of MOAP-1 expression as presented.
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Figure 8: MOAP-1 can inhibit tumor formation driven by HCT116 colon cancer cells in vivo. HCT116 colon cancer cells with overexpressed proteins (A and B) or with shRNA to MOAP-1 (C) were generated by transient transfection with the indicated expression vectors. Cells were prepared and injected into nude mice as in Fig. 9. For HCT116 cells, the p value between vector and HA-RASSF1A and vector and Myc-MOAP-1 was 0.0026 and 0.0043, respectively; n = 10–16 for all. B, middle, expression of the indicated constructs are shown as well as mouse and tumor images, B, far right, representative tumors at day 35 of tumor growth. A, tumor images were captured using a multispectral FX instrument from Carestream to support the use of stable expression of GFP constructs for this assay. MOAP-1 shRNA in C results in >70% loss of MOAP-1 expression as presented.
Mentions: To directly validate the tumor suppressor function of MOAP-1 in vivo, xenograft tumor assays were performed in athymic nude mice lacking a functioning immune system (25). To carry out these assays, we selected cancer cell lines with reduced or absent MOAP-1 expression (DAOY medulloblastoma cells, SKOV3 and H1299) or with a detectable amount of MOAP-1 (HCT116 cells). Myc-MOAP-1 was transiently expressed in DAOY medulloblastoma cells, SKOV3 (stable expression, ovarian cancer) (Fig. 7, A and B), or H1299 (stable expression, lung cancer, Fig. 7, C and D) and transiently in HCT116 colon cancer cells (Fig. 8, A and B). Following subcutaneous injection of these cells into the left and right flanks of athymic mice, a significant difference in the growth of tumors containing overexpressed Myc-MOAP-1 emerged for all cell lines tested when compared with tumors containing a control vector. This suggested a role for MOAP-1 in growth suppression. Interestingly, the loss of the function of the BH3 domain of MOAP-1 (either as a deletion or mutation) resulted in the inability to suppress tumor formation to suggest a significant dependence of MOAP-1 on its pro-apoptotic function to carry out tumor suppression (Fig. 7, C and D). Complementary to our overexpressed cells, shRNA knockdown of MOAP-1 resulted in a significant increase in tumor formation following subcutaneous injection of HCT116 cells containing shRNA to MOAP-1 (Fig. 8C). Not surprisingly, tumor formation was additionally reduced in the presence of HA-RASSF1A (for DAOY and H1299 cells, Fig. 7, B and C) suggesting a requirement for the RASSF1A/MOAP-1 apoptotic pathway in inhibiting tumor formation in these cell lines.

Bottom Line: It is an integral partner to the tumor suppressor protein, Ras association domain family 1A (RASSF1A), and functions to activate the Bcl-2 family pro-apoptotic protein Bax.Although RASSF1A is now considered a bona fide tumor suppressor protein, the role of MOAP-1 as a tumor suppressor protein has yet to be determined.Overexpression of MOAP-1 in several cancer cell lines resulted in reduced tumorigenesis and up-regulation of genes involved in cancer regulatory pathways that include apoptosis (p53, Fas, and MST1), DNA damage control (poly(ADP)-ribose polymerase and ataxia telangiectasia mutated), those within the cell metabolism (IR-α, IR-β, and AMP-activated protein kinase), and a stabilizing effect on microtubules.

View Article: PubMed Central - PubMed

Affiliation: From the Departments of Biochemistry and.

Show MeSH
Related in: MedlinePlus