TY - JOUR
T1 - Abstract 4288: RASSF1C, unlike RASSF1A, reduces TNF-α induced phosphorylation of MST1/2.
AU - Amaar, Yousef G.
AU - Firek, Matthew
AU - Reeves, Mark E.
N1 - Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Introduction: Recently, RASSF1A has been shown to mediate the apoptotic effects of TNF-α by interacting with the mammalian sterile 20-like kinase 1 and 2 (MST1/2) through the Salvador/Rassf/Hippo (SARAH) domain leading to MST1/2 phosphorylation activation of apoptosis through the Hippo pathway.
PY - 2013/4/15
Y1 - 2013/4/15
N2 - Introduction: Recently, RASSF1A has been shown to mediate the apoptotic effects of TNF-α by interacting with the mammalian sterile 20-like kinase 1 and 2 (MST1/2) through the Salvador/Rassf/Hippo (SARAH) domain leading to MST1/2 phosphorylation activation of apoptosis through the Hippo pathway. In contrast, we have previously shown that RASSF1C promotes cell proliferation and attenuates apoptosis in cancer cells. Since both RASSF1A and RASSF1C contain the SARAH domain located in their identical C-termini, RASSF1C should be capable of interacting with SARAH domain-containing proteins, and could potentially attenuate MST1/2-mediated apoptosis through the Hippo pathway. Thus, in this study we have investigated the impact of RASSF1C on MST1/2 activation/phosphorylation in presence of TNF-α, including whether RASSF1C modulates MST1/2 pro-apoptotic effects through the Hippo pathway differently from RASSF1A.Method: Breast and lung cancer cells over-expressing RASSF1A and RASSF1C were used in this study. Cells were cultured in the proper media and treated with TNF-α for 12-18 hr. Cells were collected and used for Western blot analysis utilizing antibodies that detect MST and p-MST antibodies.Results: Our preliminary data suggest that RASSF1C over-expression decreases the phosphorylation levels of MST1/2 in TNF-α-treated breast and lung cancer cells compared to those cells over-expressing RASSF1AConclusion: Our findings suggest that over-expression of RASSF1C in breast and lung cancer cells may attenuate the MST1/2 apoptotic effects by sequestering of MST1/2 proteins and inhibiting their activation by phosphorylation. The findings also further support our hypothesis that RASSF1C attenuates apoptosis; and RASSF1C, unlike RASSF1A, may inhibit MST1/2 activation and hence may negatively modulate the Hippo pathway.Citation Format: Yousef G. Amaar, Matthew Firek, Mark E. Reeves. RASSF1C, unlike RASSF1A, reduces TNF-α induced phosphorylation of MST1/2. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4288. doi:10.1158/1538-7445.AM2013-4288
AB - Introduction: Recently, RASSF1A has been shown to mediate the apoptotic effects of TNF-α by interacting with the mammalian sterile 20-like kinase 1 and 2 (MST1/2) through the Salvador/Rassf/Hippo (SARAH) domain leading to MST1/2 phosphorylation activation of apoptosis through the Hippo pathway. In contrast, we have previously shown that RASSF1C promotes cell proliferation and attenuates apoptosis in cancer cells. Since both RASSF1A and RASSF1C contain the SARAH domain located in their identical C-termini, RASSF1C should be capable of interacting with SARAH domain-containing proteins, and could potentially attenuate MST1/2-mediated apoptosis through the Hippo pathway. Thus, in this study we have investigated the impact of RASSF1C on MST1/2 activation/phosphorylation in presence of TNF-α, including whether RASSF1C modulates MST1/2 pro-apoptotic effects through the Hippo pathway differently from RASSF1A.Method: Breast and lung cancer cells over-expressing RASSF1A and RASSF1C were used in this study. Cells were cultured in the proper media and treated with TNF-α for 12-18 hr. Cells were collected and used for Western blot analysis utilizing antibodies that detect MST and p-MST antibodies.Results: Our preliminary data suggest that RASSF1C over-expression decreases the phosphorylation levels of MST1/2 in TNF-α-treated breast and lung cancer cells compared to those cells over-expressing RASSF1AConclusion: Our findings suggest that over-expression of RASSF1C in breast and lung cancer cells may attenuate the MST1/2 apoptotic effects by sequestering of MST1/2 proteins and inhibiting their activation by phosphorylation. The findings also further support our hypothesis that RASSF1C attenuates apoptosis; and RASSF1C, unlike RASSF1A, may inhibit MST1/2 activation and hence may negatively modulate the Hippo pathway.Citation Format: Yousef G. Amaar, Matthew Firek, Mark E. Reeves. RASSF1C, unlike RASSF1A, reduces TNF-α induced phosphorylation of MST1/2. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4288. doi:10.1158/1538-7445.AM2013-4288
UR - http://cancerres.aacrjournals.org/content/73/8_Supplement/4288
U2 - 10.1158/1538-7445.AM2013-4288
DO - 10.1158/1538-7445.AM2013-4288
M3 - Meeting abstract
VL - 73
SP - 4288
EP - 4288
JO - Cancer Research
JF - Cancer Research
IS - 8_Supplement
ER -