title: MYC-nick promotes cell migration by inducing fascin expression and Cdc42 activation.
abstract: MYC-nick is a cytoplasmic, transcriptionally inactive member of the MYC oncoprotein family, generated by a proteolytic cleavage of full-length MYC. MYC-nick promotes migration and survival of cells in response to chemotherapeutic agents or withdrawal of glucose. Here we report that MYC-nick is abundant in colonic and intestinal tumors derived from mouse models with mutations in the Wnt, TGF-β, and PI3K pathways. Moreover, MYC-nick is elevated in colon cancer cells deleted for FBWX7, which encodes the major E3 ligase of full-length MYC frequently mutated in colorectal cancers. MYC-nick promotes the migration of colon cancer cells assayed in 3D cultures or grown as xenografts in a zebrafish metastasis model. MYC-nick accelerates migration by activating the Rho GTPase Cdc42 and inducing fascin expression. MYC-nick, fascin, and Cdc42 are frequently up-regulated in cells present at the invasive front of human colorectal tumors, suggesting a coordinated role for these proteins in tumor migration.
authors: Division of Basic Sciences, Fred Hutchinson Cancer Research Center A2-025, Seattle, WA 98109;
authors: Sarah
authors: S
authors: Anderson
authors: Division of Basic Sciences, Fred Hutchinson Cancer Research Center A2-025, Seattle, WA 98109;
authors: Kumud Raj
authors: KR
authors: Poudel
authors: Division of Basic Sciences, Fred Hutchinson Cancer Research Center A2-025, Seattle, WA 98109;
authors: Minna
authors: M
authors: Roh-Johnson
authors: Nikolaus-Fiebiger-Center for Molecular Medicine, University Erlangen-Nuernberg, 91054 Erlangen, Germany;
authors: Thomas
authors: T
authors: Brabletz
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center D4-100, Seattle, WA 98109;
authors: Ming
authors: M
authors: Yu
authors: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039;
authors: Nofit
authors: N
authors: Borenstein-Auerbach
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center D4-100, Seattle, WA 98109; Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195;
authors: William N
authors: WN
authors: Grady
authors: Division of Basic Sciences, Fred Hutchinson Cancer Research Center A2-025, Seattle, WA 98109;
authors: Jihong
authors: J
authors: Bai
authors: Division of Basic Sciences, Fred Hutchinson Cancer Research Center A2-025, Seattle, WA 98109;
authors: Cecilia B
authors: CB
authors: Moens
authors: Division of Basic Sciences, Fred Hutchinson Cancer Research Center A2-025, Seattle, WA 98109; eisenman@fhcrc.org maralice.conaccisorrell@utsouthwestern.edu.
authors: Robert N
authors: RN
authors: Eisenman
authors: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039; Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039 eisenman@fhcrc.org maralice.conaccisorrell@utsouthwestern.edu.
authors: Maralice
authors: M
authors: Conacci-Sorrell
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D000073979:F-Box-WD Repeat-Containing Protein 7 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics*; D009362:Neoplasm Metastasis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D015533:Transcriptional Activation / Q000235:genetics; D015027:Zebrafish; D020764:cdc42 GTP-Binding Protein / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; C489427:MYC protein, human; D008840:Microfilament Proteins; D016271:Proto-Oncogene Proteins c-myc; C020324:fascin; D020764:cdc42 GTP-Binding Protein
keywords: MYC; MYC-nick; colon cancer; fascin; motility