Minireview: Mouse Models of Rho GTPase Function in Mammary Gland Development, Tumorigenesis, and Metastasis

Overview

Journal Mol Endocrinol

Specialties Endocrinology
Molecular Biology

Date 2015 Dec 19

PMID 26677753

Citations 10

Authors

Yan Zuo

Wonkyung Oh

Arzu Ulu

Jeffrey A Frost

Affiliations

Soon will be listed here.

Abstract

Ras homolog (Rho) family small GTPases are critical regulators of actin cytoskeletal organization, cell motility, proliferation, and survival. Surprisingly, the large majority of the studies underlying our knowledge of Rho protein function have been carried out in cultured cells, and it is only recently that researchers have begun to assess Rho GTPase regulation and function in vivo. The purpose of this review is to evaluate our current knowledge of Rho GTPase function in mouse mammary gland development, tumorigenesis and metastasis. Although our knowledge is still incomplete, these studies are already uncovering important themes as to the physiological roles of Rho GTPase signaling in normal mammary gland development and function. Essential contributions of Rho proteins to breast cancer initiation, tumor progression, and metastatic dissemination have also been identified.

Citing Articles

Distinct Requirements for Adaptor Proteins NCK1 and NCK2 in Mammary Gland Development.

Golding A, Ferrier B, New L, Lu P, Martin C, Shata E J Mammary Gland Biol Neoplasia. 2023; 28(1):19.

PMID: 37479911 PMC: 10361900. DOI: 10.1007/s10911-023-09541-1.

TF-Prioritizer: a Java pipeline to prioritize condition-specific transcription factors.

Hoffmann M, Trummer N, Schwartz L, Jankowski J, Lee H, Willruth L Gigascience. 2023; 12.

PMID: 37132521 PMC: 10155229. DOI: 10.1093/gigascience/giad026.

Nucleoporin-93 reveals a common feature of aggressive breast cancers: robust nucleocytoplasmic transport of transcription factors.

Nataraj N, Noronha A, Lee J, Ghosh S, Mohan Raju H, Sekar A Cell Rep. 2022; 38(8):110418.

PMID: 35196484 PMC: 8957480. DOI: 10.1016/j.celrep.2022.110418.

Rho GTPases: Big Players in Breast Cancer Initiation, Metastasis and Therapeutic Responses.

Humphries B, Wang Z, Yang C Cells. 2020; 9(10).

PMID: 32992837 PMC: 7600866. DOI: 10.3390/cells9102167.

Influence of Fibroblasts on Mammary Gland Development, Breast Cancer Microenvironment Remodeling, and Cancer Cell Dissemination.

Avagliano A, Fiume G, Ruocco M, Martucci N, Vecchio E, Insabato L Cancers (Basel). 2020; 12(6).

PMID: 32604738 PMC: 7352995. DOI: 10.3390/cancers12061697.

References

Jadeski L, Mataraza J, Jeong H, Li Z, Sacks D . IQGAP1 stimulates proliferation and enhances tumorigenesis of human breast epithelial cells. J Biol Chem. 2007; 283(2):1008-17. DOI: 10.1074/jbc.M708466200. View

Ye D, Field J . PAK signaling in cancer. Cell Logist. 2012; 2(2):105-116. PMC: 3490961. DOI: 10.4161/cl.21882. View

Hakem A, Sanchez-Sweatman O, You-Ten A, Duncan G, Wakeham A, Khokha R . RhoC is dispensable for embryogenesis and tumor initiation but essential for metastasis. Genes Dev. 2005; 19(17):1974-9. PMC: 1199568. DOI: 10.1101/gad.1310805. View

Chakravarty G, Hadsell D, Buitrago W, Settleman J, Rosen J . p190-B RhoGAP regulates mammary ductal morphogenesis. Mol Endocrinol. 2003; 17(6):1054-65. DOI: 10.1210/me.2002-0428. View

Liu S, Goldstein R, Scepansky E, Rosenblatt M . Inhibition of rho-associated kinase signaling prevents breast cancer metastasis to human bone. Cancer Res. 2009; 69(22):8742-51. DOI: 10.1158/0008-5472.CAN-09-1541. View

Goodison S, Yuan J, Sloan D, Kim R, Li C, Popescu N . The RhoGAP protein DLC-1 functions as a metastasis suppressor in breast cancer cells. Cancer Res. 2005; 65(14):6042-53. PMC: 1360170. DOI: 10.1158/0008-5472.CAN-04-3043. View

Gligorijevic B, Wyckoff J, Yamaguchi H, Wang Y, Roussos E, Condeelis J . N-WASP-mediated invadopodium formation is involved in intravasation and lung metastasis of mammary tumors. J Cell Sci. 2012; 125(Pt 3):724-34. PMC: 3367832. DOI: 10.1242/jcs.092726. View

Sternlicht M . Key stages in mammary gland development: the cues that regulate ductal branching morphogenesis. Breast Cancer Res. 2006; 8(1):201. PMC: 1413974. DOI: 10.1186/bcr1368. View

Liao Y, Ruan J, Lua I, Li M, Chen W, Wang J . Overexpressed hPTTG1 promotes breast cancer cell invasion and metastasis by regulating GEF-H1/RhoA signalling. Oncogene. 2011; 31(25):3086-97. PMC: 3381367. DOI: 10.1038/onc.2011.476. View

10.

Burbelo P, Miyamoto S, Utani A, Brill S, Yamada K, Hall A . p190-B, a new member of the Rho GAP family, and Rho are induced to cluster after integrin cross-linking. J Biol Chem. 1995; 270(52):30919-26. DOI: 10.1074/jbc.270.52.30919. View

11.

Medale-Giamarchi C, Lajoie-Mazenc I, Malissein E, Meunier E, Couderc B, Berge Y . RhoB modifies estrogen responses in breast cancer cells by influencing expression of the estrogen receptor. Breast Cancer Res. 2013; 15(1):R6. PMC: 3672819. DOI: 10.1186/bcr3377. View

12.

Eswaran J, Li D, Shah A, Kumar R . Molecular pathways: targeting p21-activated kinase 1 signaling in cancer--opportunities, challenges, and limitations. Clin Cancer Res. 2012; 18(14):3743-9. PMC: 3399091. DOI: 10.1158/1078-0432.CCR-11-1952. View

13.

Sosa M, Lopez-Haber C, Yang C, Wang H, Lemmon M, Busillo J . Identification of the Rac-GEF P-Rex1 as an essential mediator of ErbB signaling in breast cancer. Mol Cell. 2010; 40(6):877-92. PMC: 3038344. DOI: 10.1016/j.molcel.2010.11.029. View

14.

Zuo Y, Berdeaux R, Frost J . The RhoGEF Net1 is required for normal mammary gland development. Mol Endocrinol. 2014; 28(12):1948-60. PMC: 4250368. DOI: 10.1210/me.2014-1128. View

15.

Chakravarty G, Roy D, Gonzales M, Gay J, Contreras A, Rosen J . P190-B, a Rho-GTPase-activating protein, is differentially expressed in terminal end buds and breast cancer. Cell Growth Differ. 2000; 11(7):343-54. View

16.

Fritz G, Just I, Kaina B . Rho GTPases are over-expressed in human tumors. Int J Cancer. 1999; 81(5):682-7. DOI: 10.1002/(sici)1097-0215(19990531)81:5<682::aid-ijc2>3.0.co;2-b. View

17.

Zhang S, Han J, Sells M, Chernoff J, Knaus U, Ulevitch R . Rho family GTPases regulate p38 mitogen-activated protein kinase through the downstream mediator Pak1. J Biol Chem. 1995; 270(41):23934-6. DOI: 10.1074/jbc.270.41.23934. View

18.

Fischer A, Stuckas H, Gluth M, Russell T, Rudolph M, Beeman N . Impaired tight junction sealing and precocious involution in mammary glands of PKN1 transgenic mice. J Cell Sci. 2007; 120(Pt 13):2272-83. DOI: 10.1242/jcs.03467. View

19.

Abo A, Qu J, Cammarano M, Dan C, Fritsch A, Baud V . PAK4, a novel effector for Cdc42Hs, is implicated in the reorganization of the actin cytoskeleton and in the formation of filopodia. EMBO J. 1998; 17(22):6527-40. PMC: 1171000. DOI: 10.1093/emboj/17.22.6527. View

20.

Citterio C, Menacho-Marquez M, Garcia-Escudero R, Larive R, Barreiro O, Sanchez-Madrid F . The rho exchange factors vav2 and vav3 control a lung metastasis-specific transcriptional program in breast cancer cells. Sci Signal. 2012; 5(244):ra71. DOI: 10.1126/scisignal.2002962. View