MSF REPROGRAMS MYOFIBROBLASTS TOWARD LACTATE PRODUCTION AND FUEL ANAERBOIC TUMOR GROWTH
Presented herein is a method for treating a subject afflicted with a tumor comprising administering to the subject a therapeutically effective amount of an agent that inhibits the MSF/Cdc42/NFkB cascade in the subject's tumor-associated fibroblasts.
1 . A method for treating a subject afflicted with a tumor comprising administering to the subject a therapeutically effective amount of an agent that inhibits the MSF/Cdc42/NFkB cascade in the subject's tumor-associated fibroblasts.
2 . The method of claim 1 , wherein the agent inhibits the MSF/Cdc42/NFkB cascade by inhibiting the activity of one or more of MSF, Cdc42 and NFkB in the subject's tumor-associated fibroblasts.
3 . The method of claim 2 , wherein the agent inhibits the activity of MSF in the subject's tumor-associated fibroblasts.
4 . The method of claim 3 , wherein the agent inhibits the activity of MSF in the subject's tumor-associated fibroblasts by interacting with the 10-amino acid residue C-terminal portion of MSF.
5 . The method of claim 2 , wherein the agent inhibits the activity of Cdc42 in the subject's tumor-associated fibroblasts.
6 . The method of claim 2 , wherein the agent inhibits the activity of NFkB in the subject's tumor-associated fibroblasts.
7 . The method of claim 2 , wherein the agent is an antibody, a polypeptide or a small molecule.
8 . The method of claim 1 , wherein the agent inhibits the MSF/Cdc42/NFkB cascade by inhibiting the expression of one or more of MSF, Cdc42 and NFkB in the subject's tumor-associated fibroblasts.
9 . The method of claim 8 , wherein the agent inhibits the expression of MSF in the subject's tumor-associated fibroblasts.
10 . The method of claim 8 , wherein the agent inhibits the expression of Cdc42 in the subject's tumor-associated fibroblasts.
11 . The method of claim 8 , wherein the agent inhibits the expression of NFkB in the subject's tumor-associated fibroblasts.
12 . The method of claim 8 , wherein the agent is a nucleic acid.
13 . The method of claim 1 , wherein the subject is human.
14 . The method of claim 1 , wherein the tumor is located in one or more of the breast, skin, kidney, lung, pancreas, rectum, colon, prostate, bladder, epithelial tissue and non-epithelial tissue.
15 . The method of claim 1 , wherein the agent is administered in the form of a pharmaceutical composition.
16 . An immortalized cell line that overexpresses MSF.
17 . The cell line of claim 16 , wherein the cell line is an hTERT-immortalized fibroblast cell line.