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Conserved Oncogenic Behavior of the FAM83 Family Regulates MAPK Signaling in Human Cancer

Conserved Oncogenic Behavior of the FAM83 Family Regulates MAPK Signaling in Human Cancer FAM83B (family with sequence similarity 83, member B) was recently identified as a novel oncogene involved in activating CRAF/MAPK signaling and driving epithelial cell transformation. FAM83B is one of eight members of a protein family (FAM83) characterized by a highly conserved domain of unknown function (DUF1669), which is necessary and sufficient to drive transformation. Here, it is demonstrated that additional FAM83 members also exhibit oncogenic properties and have significantly elevated levels of expression in multiple human tumor types using a TissueScan Cancer Survey Panel PCR array and database mining. Furthermore, modeling the observed tumor expression of FAM83A, FAM83C, FAM83D, or FAM83E promoted human mammary epithelial cell (HMEC) transformation, which correlated with the ability of each FAM83 member to bind CRAF (RAF1) and promote CRAF membrane localization. Conversely, ablation of FAM83A or FAM83D from breast cancer cells resulted in diminished MAPK signaling with marked suppression of growth in vitro and tumorigenicity in vivo . Importantly, each FAM83 member was determined to be elevated in at least one of 17 distinct tumor types examined, with FAM83A , FAM83B , and FAM83D most frequently overexpressed in several diverse tissue types. Finally, evidence suggests that elevated expression of FAM83 members is associated with elevated tumor grade and decreased overall survival. Implications: FAM83 proteins represent a novel family of oncogenes suitable for the development of cancer therapies aimed at suppressing MAPK signaling. Mol Cancer Res; 12(8); 1156–65. ©2014 AACR . http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular Cancer Research American Association of Cancer Research

Conserved Oncogenic Behavior of the FAM83 Family Regulates MAPK Signaling in Human Cancer

Conserved Oncogenic Behavior of the FAM83 Family Regulates MAPK Signaling in Human Cancer

Molecular Cancer Research , Volume 12 (8): 1156 – Aug 1, 2014

Abstract

FAM83B (family with sequence similarity 83, member B) was recently identified as a novel oncogene involved in activating CRAF/MAPK signaling and driving epithelial cell transformation. FAM83B is one of eight members of a protein family (FAM83) characterized by a highly conserved domain of unknown function (DUF1669), which is necessary and sufficient to drive transformation. Here, it is demonstrated that additional FAM83 members also exhibit oncogenic properties and have significantly elevated levels of expression in multiple human tumor types using a TissueScan Cancer Survey Panel PCR array and database mining. Furthermore, modeling the observed tumor expression of FAM83A, FAM83C, FAM83D, or FAM83E promoted human mammary epithelial cell (HMEC) transformation, which correlated with the ability of each FAM83 member to bind CRAF (RAF1) and promote CRAF membrane localization. Conversely, ablation of FAM83A or FAM83D from breast cancer cells resulted in diminished MAPK signaling with marked suppression of growth in vitro and tumorigenicity in vivo . Importantly, each FAM83 member was determined to be elevated in at least one of 17 distinct tumor types examined, with FAM83A , FAM83B , and FAM83D most frequently overexpressed in several diverse tissue types. Finally, evidence suggests that elevated expression of FAM83 members is associated with elevated tumor grade and decreased overall survival. Implications: FAM83 proteins represent a novel family of oncogenes suitable for the development of cancer therapies aimed at suppressing MAPK signaling. Mol Cancer Res; 12(8); 1156–65. ©2014 AACR .

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Publisher
American Association of Cancer Research
Copyright
Copyright © 2014 American Association for Cancer Research
ISSN
1541-7786
eISSN
1557-3125
DOI
10.1158/1541-7786.MCR-13-0289
pmid
24736947
Publisher site
See Article on Publisher Site

Abstract

FAM83B (family with sequence similarity 83, member B) was recently identified as a novel oncogene involved in activating CRAF/MAPK signaling and driving epithelial cell transformation. FAM83B is one of eight members of a protein family (FAM83) characterized by a highly conserved domain of unknown function (DUF1669), which is necessary and sufficient to drive transformation. Here, it is demonstrated that additional FAM83 members also exhibit oncogenic properties and have significantly elevated levels of expression in multiple human tumor types using a TissueScan Cancer Survey Panel PCR array and database mining. Furthermore, modeling the observed tumor expression of FAM83A, FAM83C, FAM83D, or FAM83E promoted human mammary epithelial cell (HMEC) transformation, which correlated with the ability of each FAM83 member to bind CRAF (RAF1) and promote CRAF membrane localization. Conversely, ablation of FAM83A or FAM83D from breast cancer cells resulted in diminished MAPK signaling with marked suppression of growth in vitro and tumorigenicity in vivo . Importantly, each FAM83 member was determined to be elevated in at least one of 17 distinct tumor types examined, with FAM83A , FAM83B , and FAM83D most frequently overexpressed in several diverse tissue types. Finally, evidence suggests that elevated expression of FAM83 members is associated with elevated tumor grade and decreased overall survival. Implications: FAM83 proteins represent a novel family of oncogenes suitable for the development of cancer therapies aimed at suppressing MAPK signaling. Mol Cancer Res; 12(8); 1156–65. ©2014 AACR .

Journal

Molecular Cancer ResearchAmerican Association of Cancer Research

Published: Aug 1, 2014

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