Shared Signaling Pathways in Normal and Breast Cancer Stem Cells

Overview

Journal J Carcinog

Publisher Biomed Central

Date 2012 Jan 27

PMID 22279423

Citations 24

Authors

Gautam K Malhotra

Xiangshan Zhao

Hamid Band

Vimla Band

Affiliations

Soon will be listed here.

Abstract

Recent advances in our understanding of breast cancer biology have led to the identification of a subpopulation of cells within tumors that appear to be responsible for initiating and propagating the cancer. These tumor initiating cells are not only unique in their ability to generate tumors, but also share many similarities with elements of normal adult tissue stem cells, and have therefore been termed cancer stem cells (CSCs). These CSCs often inappropriately use many of the same signaling pathways utilized by their normal stem cell counterparts which may present a challenge to the development of CSC specific therapies. Here, we discuss three major stem cell signaling pathways (Notch, Wnt, and Hedgehog); with a focus on their function in normal mammary gland development and their misuse in breast cancer stem cell fate determination.

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References

Angers S, Moon R . Proximal events in Wnt signal transduction. Nat Rev Mol Cell Biol. 2009; 10(7):468-77. DOI: 10.1038/nrm2717. View

Al-Hajj M, Wicha M, Benito-Hernandez A, Morrison S, Clarke M . Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci U S A. 2003; 100(7):3983-8. PMC: 153034. DOI: 10.1073/pnas.0530291100. View

Micchelli C, The I, Selva E, Mogila V, Perrimon N . Rasp, a putative transmembrane acyltransferase, is required for Hedgehog signaling. Development. 2002; 129(4):843-51. DOI: 10.1242/dev.129.4.843. View

He B, Reguart N, You L, Mazieres J, Xu Z, Lee A . Blockade of Wnt-1 signaling induces apoptosis in human colorectal cancer cells containing downstream mutations. Oncogene. 2005; 24(18):3054-8. DOI: 10.1038/sj.onc.1208511. View

Liu S, Dontu G, Mantle I, Patel S, Ahn N, Jackson K . Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res. 2006; 66(12):6063-71. PMC: 4386278. DOI: 10.1158/0008-5472.CAN-06-0054. View

Hanahan D, Weinberg R . The hallmarks of cancer. Cell. 2000; 100(1):57-70. DOI: 10.1016/s0092-8674(00)81683-9. View

Ronchini C, Capobianco A . Induction of cyclin D1 transcription and CDK2 activity by Notch(ic): implication for cell cycle disruption in transformation by Notch(ic). Mol Cell Biol. 2001; 21(17):5925-34. PMC: 87311. DOI: 10.1128/MCB.21.17.5925-5934.2001. View

Tsukamoto A, Grosschedl R, Guzman R, Parslow T, Varmus H . Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice. Cell. 1988; 55(4):619-25. DOI: 10.1016/0092-8674(88)90220-6. View

McMahon A, Ingham P, Tabin C . Developmental roles and clinical significance of hedgehog signaling. Curr Top Dev Biol. 2003; 53:1-114. DOI: 10.1016/s0070-2153(03)53002-2. View

10.

Mukherjee S, Frolova N, Sadlonova A, Novak Z, Steg A, Page G . Hedgehog signaling and response to cyclopamine differ in epithelial and stromal cells in benign breast and breast cancer. Cancer Biol Ther. 2006; 5(6):674-83. PMC: 1557635. DOI: 10.4161/cbt.5.6.2906. View

11.

Moraes R, Chang H, Harrington N, Landua J, Prigge J, Lane T . Ptch1 is required locally for mammary gland morphogenesis and systemically for ductal elongation. Development. 2009; 136(9):1423-32. PMC: 2675781. DOI: 10.1242/dev.023994. View

12.

Leong K, Niessen K, Kulic I, Raouf A, Eaves C, Pollet I . Jagged1-mediated Notch activation induces epithelial-to-mesenchymal transition through Slug-induced repression of E-cadherin. J Exp Med. 2007; 204(12):2935-48. PMC: 2118507. DOI: 10.1084/jem.20071082. View

13.

Brennan K, Brown A . Wnt proteins in mammary development and cancer. J Mammary Gland Biol Neoplasia. 2004; 9(2):119-31. DOI: 10.1023/B:JOMG.0000037157.94207.33. View

14.

Dievart A, Beaulieu N, Jolicoeur P . Involvement of Notch1 in the development of mouse mammary tumors. Oncogene. 1999; 18(44):5973-81. DOI: 10.1038/sj.onc.1202991. View

15.

Jhappan C, Gallahan D, Stahle C, Chu E, Smith G, Merlino G . Expression of an activated Notch-related int-3 transgene interferes with cell differentiation and induces neoplastic transformation in mammary and salivary glands. Genes Dev. 1992; 6(3):345-55. DOI: 10.1101/gad.6.3.345. View

16.

Lewis M, Ross S, Strickland P, Sugnet C, Jimenez E, Scott M . Defects in mouse mammary gland development caused by conditional haploinsufficiency of Patched-1. Development. 1999; 126(22):5181-93. DOI: 10.1242/dev.126.22.5181. View

17.

Stylianou S, Clarke R, Brennan K . Aberrant activation of notch signaling in human breast cancer. Cancer Res. 2006; 66(3):1517-25. DOI: 10.1158/0008-5472.CAN-05-3054. View

18.

Gallahan D, Jhappan C, Robinson G, Hennighausen L, Sharp R, Kordon E . Expression of a truncated Int3 gene in developing secretory mammary epithelium specifically retards lobular differentiation resulting in tumorigenesis. Cancer Res. 1996; 56(8):1775-85. View

19.

Brisken C, Heineman A, Chavarria T, Elenbaas B, Tan J, Dey S . Essential function of Wnt-4 in mammary gland development downstream of progesterone signaling. Genes Dev. 2000; 14(6):650-4. PMC: 316462. View

20.

Wolf I, Bose S, Desmond J, Lin B, Williamson E, Karlan B . Unmasking of epigenetically silenced genes reveals DNA promoter methylation and reduced expression of PTCH in breast cancer. Breast Cancer Res Treat. 2007; 105(2):139-55. DOI: 10.1007/s10549-006-9440-4. View