专题论文

粉红丝带引发的思考——Wnt信号通路在乳腺发育与乳腺癌变中的角色

  • 俞清 ,
  • 曾艺
展开
  • 中国科学院上海生命科学研究院生物化学与细胞生物学研究所, 细胞生物学国家重点实验室, 上海 200031
俞清,博士后,研究方向为成体干细胞,电子信箱:cissyyu@sibcb.ac.cn

收稿日期: 2016-09-11

  修回日期: 2016-10-05

  网络出版日期: 2016-11-05

Mammary development and breast cancer: A Wnt prospective

  • YU Qing ,
  • ZENG Yi
Expand
  • State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

Received date: 2016-09-11

  Revised date: 2016-10-05

  Online published: 2016-11-05

摘要

Wnt信号转导通路是参与乳腺发育和肿瘤形成的重要机制。本文综述了Wnt信号转导通路调控乳腺发育和干细胞稳态研究的进展,讨论了Wnt信号转导中成员分子在乳腺癌形成中的角色。

本文引用格式

俞清 , 曾艺 . 粉红丝带引发的思考——Wnt信号通路在乳腺发育与乳腺癌变中的角色[J]. 科技导报, 2016 , 34(20) : 5 -13 . DOI: 10.3981/j.issn.1000-7857.2016.20.001

Abstract

The Wnt pathway has emerged as a key signaling cascade participating in mammary organogenesis and breast oncogenesis. This paper reviews the current knowledge of how the pathway regulates the stem cells and the normal development of the mammary gland, and how its various components contribute to the breast carcinoma pathology.

参考文献

[1] Bittner J J. Some possible effects of nursing on the mammary gland tumor incidence in mice[J]. Science, 1936, 84:162-169.
[2] Korteweg R. Genetically determined differences in hormone production a possible factor influencing the susceptibility to mammary cancer in mice[J]. British Journal of Cancer, 1948(2):91-94.
[3] Lyons M J, Moore D H. Purification of the mouse mammary tumour virus[J]. Nature, 1962, 194:1141-1142.
[4] Nusse R, Varmus H E. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome[J]. Cell, 1982, 31:99-109.
[5] Clevers H, Nusse R. Wnt/beta-catenin signaling and disease[J]. Cell, 2012, 149:1192-1205.
[6] Eastman Q, Grosschedl R. Regulation of LEF-1/TCF transcription factors by Wnt and other signals[J]. Current Opinion in Cell Biology, 1999, 11:233-240.
[7] Schambony A, Kunz M, Gradl D. Cross-regulation of Wnt signaling and cell adhesion[J]. Differentiation, 2004, 72(7):307-318.
[8] Kuhl M, Sheldahl L C, Malbon C C, et al. Ca(2+)/calmodulin-dependent protein kinase Ⅱ is stimulated by Wnt and Frizzled homologs and promotes ventral cell fates in Xenopus[J]. Journal of Biological Chemistry, 2000, 275:12701-12711.
[9] Minami Y, Oishi I, Endo M, et al. Ror-family receptor tyrosine kinases in noncanonical Wnt signaling:Their implications in developmental morphogenesis and human diseases[J]. Developmental Dynamics, 2010, 239:1-15.
[10] Veltmaat J M, Van Veelen W, Thiery J P, et al. Identification of the mammary line in mouse by Wnt10b expression[J]. Developmental Dynamics, 2004, 229:349-356.
[11] Gu B, Sun P, Yuan Y, et al. Pygo2 expands mammary progenitor cells by facilitating histone H3 K4 methylation[J]. Journal of Cell Biology, 2009, 185:811-826.
[12] Lindvall C, Evans N C, Zylstra C R, et al. The Wnt signaling receptor Lrp5 is required for mammary ductal stem cell activity and Wnt1-induced tumorigenesis[J]. Journal of Biological Chemistry, 2006, 281:35081-35087.
[13] Lindvall C, Zylstra C R, Evans N, et al. The Wnt co-receptor Lrp6 is required for normal mouse mammary gland development[J]. PloS One, 2009, 4:e5813.
[14] van Genderen C, Okamura R M, Farinas I, et al. Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice[J]. Genes & Development, 1994, 8:2691-2703.
[15] Macias H, Hinck L. Mammary gland development. Wiley interdisciplinary reviews[J]. Developmental Biology, 2012, 1:533-557.
[16] Buhler T A, Dale T C, Kieback C, et al. Localization and quantification of Wnt-2 gene expression in mouse mammary development[J]. Developmental Biology, 1993, 155:87-96.
[17] Cai C, Yu Q C, Jiang W, et al. R-spondin1 is a novel hormone mediator for mammary stem cell self-renewal[J]. Genes & Development, 2014, 28:2205-2218.
[18] Visvader J E. Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis[J]. Genes & Development, 2009, 23:2563-2577.
[19] Deome K B, Faulkin L J, Jr, Bern H A, et al. Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland-free mammary fat pads of female C3H mice[J]. Cancer Research, 1959, 19:515-520.
[20] Stingl J, Eirew P, Ricketson I, et al. Purification and unique properties of mammary epithelial stem cells[J]. Nature, 2006, 439:993-997.
[21] Eirew P, Stingl J, Raouf A, et al. A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability[J]. Nature Medicine, 2008, 14:1384-1389.
[22] Lim E, Vaillant F, Wu D, et al. Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers[J]. Nature Medicine, 2009, 15:907-913.
[23] Wang D, Cai C, Dong X, et al. Identification of multipotent mammary stem cells by protein C receptor expression[J]. Nature, 2015, 517:81-84.
[24] Zeng Y A, Nusse R. Wnt proteins are self-renewal factors for mammary stem cells and promote their long-term expansion in culture[J]. Cell Stem Cell, 2010, 6:568-577.
[25] Roarty K, Shore A N, Creighton C J, et al. Ror2 regulates branching, differentiation, and actin-cytoskeletal dynamics within the mammary epithelium[J]. Journal of Cell Biology, 2015, 208:351-366.
[26] van Amerongen R, Bowman A N, Nusse R. Developmental stage and time dictate the fate of Wnt/beta-catenin-responsive stem cells in the mammary gland[J]. Cell Stem Cell, 2012, 11:387-400.
[27] Li L, Clevers H. Coexistence of quiescent and active adult stem cells in mammals[J]. Science, 2010, 327:542-545.
[28] Srinivasan K, Strickland P, Valdes A, et al. Netrin-1/neogenin interaction stabilizes multipotent progenitor cap cells during mammary gland morphogenesis[J]. Developmental Cell, 2003, 4:371-382.
[29] Williams J M, Daniel C W. Mammary ductal elongation:Differentiation of myoepithelium and basal lamina during branching morphogenesis[J]. Developmental Biology, 1983, 97:274-290.
[30] Zeng L, Cai C, Li S, et al. Essential roles of cyclin Y-like 1 and cyclin Y in dividing Wnt-responsive mammary stem/progenitor cells[J]. PLoS Genetics, 2016, 12:e1006055.
[31] Davidson G, Shen J, Huang Y L, et al. Cell cycle control of wnt receptor activation[J]. Developmental Cell, 2009, 17:788-799.
[32] Jiang M, Gao Y, Yang T, et al. Cyclin Y, a novel membrane-associated cyclin, interacts with PFTK1[J]. FEBS Letters, 2009, 583:2171-2178.
[33] Macias H, Moran A, Samara Y, et al. SLIT/ROBO1 signaling suppresses mammary branching morphogenesis by limiting basal cell number[J]. Developmental Cell, 2011, 20:827-840.
[34] Strickland P, Shin G C, Plump A, et al. Slit2 and netrin 1 act synergistically as adhesive cues to generate tubular bi-layers during ductal morphogenesis[J]. Development, 2006, 133:823-832.
[35] Harburg G, Compton J, Liu W, et al. SLIT/ROBO2 signaling promotes mammary stem cell senescence by inhibiting Wnt signaling[J]. Stem Cell Reports, 2014, 3:385-393.
[36] Chakrabarti R, Wei Y, Hwang J, et al. DeltaNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signalling[J]. Nature Cell Biology, 2014, 16:1004-1015.
[37] Gu B, Watanabe K, Sun P, et al. Chromatin effector Pygo2 mediates Wnt-notch crosstalk to suppress luminal/alveolar potential of mammary stem and basal cells[J]. Cell Stem Cell, 2013, 13:48-61.
[38] Fu N, Lindeman G J, Visvader J E. The mammary stem cell hierarchy[J]. Current Topics in Developmental Biology, 2014, 107:133-160.
[39] Visvader J E, Stingl J. Mammary stem cells and the differentiation hierarchy:Current status and perspectives[J]. Genes & Development, 2014, 28:1143-1158.
[40] Barker N, van Es J H, Kuipers J, et al. Identification of stem cells in small intestine and colon by marker gene Lgr5[J]. Nature, 2007, 449:1003-1007.
[41] de Visser K E, Ciampricotti M, Michalak E M, et al. Developmental stage-specific contribution of LGR5(+) cells to basal and luminal epithelial lineages in the postnatal mammary gland[J]. Journal of Pathology, 2012, 228:300-309.
[42] Zhang M Z, Ferrigno O, Wang Z, et al. TGIF governs a feed-forward network that empowers Wnt signaling to drive mammary tumorigenesis[J]. Cancer Cell, 2015, 27:547-560.
[43] Prater M D, Petit V, Alasdair Russell I, et al. Mammary stem cells have myoepithelial cell properties[J]. Nature Cell Biology, 2014, 16:942-950.
[44] Rios A C, Fu N Y, Lindeman G J, et al. In situ identification of bipotent stem cells in the mammary gland[J]. Nature, 2014, 506:322-327.
[45] Van Keymeulen A, Rocha A S, Ousset M, et al. Distinct stem cells contribute to mammary gland development and maintenance[J]. Nature, 2011, 479:189-193.
[46] Lane T F, Leder P. Wnt-10b directs hypermorphic development and transformation in mammary glands of male and female mice[J]. Oncogene, 1997, 15:2133-2144.
[47] Incassati A, Chandramouli A, Eelkema R, et al. Key signaling nodes in mammary gland development and cancer:Beta-catenin[J]. Breast Cancer Research:BCR, 2010, 12:213.
[48] Lowther W, Wiley K, Smith G H, et al. A new common integration site, Int7, for the mouse mammary tumor virus in mouse mammary tumors identifies a gene whose product has furin-like and thrombospondin-like sequences[J]. Journal of Virology, 2005, 79:10093-10096.
[49] Theodorou V, Kimm M A, Boer M, et al. MMTV insertional mutagenesis identifies genes, gene families and pathways involved in mammary cancer[J]. Nature Genetics, 2007, 39:759-769.
[50] Klauzinska M, Baljinnyam B, Raafat A, et al. Rspo2/Int7 regulates invasiveness and tumorigenic properties of mammary epithelial cells[J]. Journal of Cellular Physiology, 2012, 227:1960-1971.
[51] Herschkowitz J I, Simin K, Weigman V J, et al. Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors[J]. Genome Biology, 2007, 8:R76. doi:10.1186/gb-2007-8-5-r76.
[52] Khramtsov A I, Khramtsova G F, Tretiakova M, et al. Wnt/beta-catenin pathway activation is enriched in basal-like breast cancers and predicts poor outcome[J]. The American Journal of Pathology, 2010, 176:2911-2920.
[53] Liu C C, Prior J, Piwnica-Worms D, et al. LRP6 overexpression defines a class of breast cancer subtype and is a target for therapy[J]. PNAS, 2010, 107:5136-5141.
[54] Foulkes W D, Smith I E, Reis-Filho J S. Triple-negative breast cancer[J]. New England Journal of Medicine, 2010, 363:1938-1948.
[55] Lehmann B D, Bauer J A, Chen X, et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies[J]. Journal of Clinical Investigation, 2011, 121:2750-2767.
[56] Lopez-Knowles E, Zardawi S J, McNeil C M, et al. Cytoplasmic localization of beta-catenin is a marker of poor outcome in breast cancer patients[J]. Cancer Epidemiology, Biomarkers & Prevention, 2010, 19:301-309.
[57] Forget M A, Turcotte S, Beauseigle D, et al. The Wnt pathway regulator DKK1 is preferentially expressed in hormone-resistant breast tumours and in some common cancer types[J]. British Journal of Cancer, 2007, 96:646-653.
[58] Niida A, Hiroko T, Kasai M, et al. DKK1, a negative regulator of Wnt signaling, is a target of the beta-catenin/TCF pathway[J]. Oncogene, 2004, 23:8520-8526.
[59] Xu W H, Liu Z B, Yang C, et al. Expression of dickkopf-1 and beta-catenin related to the prognosis of breast cancer patients with triple negative phenotype[J]. PLoS One, 2012, 7:e37624.
[60] Furuuchi K, Tada M, Yamada H, et al. Somatic mutations of the APC gene in primary breast cancers[J]. The American Journal of Pathology, 2000, 156:1997-2005.
[61] Sorlie T, Bukholm I, Borresen-Dale A L. Truncating somatic mutation in exon 15 of the APC gene is a rare event in human breast carcinomas. Mutations in brief no. 179. Online[J]. Human Mutation, 1998, 12:215.
[62] Ozaki S, Ikeda S, Ishizaki Y, et al. Alterations and correlations of the components in the Wnt signaling pathway and its target genes in breast cancer[J]. Oncology Reports, 2005, 14:1437-1443.
[63] Prasad C P, Mirza S, Sharma G, et al. Epigenetic alterations of CDH1 and APC genes:Relationship with activation of Wnt/beta-catenin pathway in invasive ductal carcinoma of breast[J]. Life Sciences, 2008, 83:318-325.
[64] Van der Auwera I, Van Laere S J, Van den Bosch S M, et al. Aberrant methylation of the Adenomatous Polyposis Coli (APC) gene promoter is associated with the inflammatory breast cancer phenotype[J]. British Journal of Cancer, 2008, 99:1735-1742.
[65] Veeck J, Wild P J, Fuchs T, et al. Prognostic relevance of Wnt-inhibitory factor1(WIF1) and Dickkopf-3(DKK3) promoter methylation in human breast cancer[J]. BMC Cancer, 2009, 9:217.
[66] Klopocki E, Kristiansen G, Wild P J, et al. Loss of SFRP1 is associated with breast cancer progression and poor prognosis in early stage tumors[J]. International Journal of Oncology, 2004, 25:641-649.
[67] Veeck J, Geisler C, Noetzel E, et al. Epigenetic inactivation of the secreted frizzled-related protein-5(SFRP5) gene in human breast cancer is associated with unfavorable prognosis[J]. Carcinogenesis, 2008, 29:991-998.
[68] Matsuda Y, Schlange T, Oakeley E J, et al. WNT signaling enhances breast cancer cell motility and blockade of the WNT pathway by sFRP1 suppresses MDA-MB-231 xenograft growth[J]. Breast cancer research:BCR, 2009, 11:R32. doi:10.1186/bcr2317.
[69] Ai L, Tao Q, Zhong S, et al. Inactivation of Wnt inhibitory factor-1(WIF1) expression by epigenetic silencing is a common event in breast cancer[J]. Carcinogenesis, 2006, 27:1341-1348.
[70] Bjorklund P, Svedlund J, Olsson A K, et al. The internally truncated LRP5 receptor presents a therapeutic target in breast cancer[J]. PLoS One, 2009, 4:e4243.
[71] Sorlie T, Tibshirani R, Parker J, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets[J]. PNAS, 2003, 100:8418-8423.
[72] Yang L, Wu X, Wang Y, et al. FZD7 has a critical role in cell proliferation in triple negative breast cancer[J]. Oncogene, 2011, 30:4437-4446.
[73] Bafico A, Liu G, Goldin L, et al. An autocrine mechanism for constitutive Wnt pathway activation in human cancer cells[J]. Cancer Cell, 2004, 6:497-506.
[74] Schlange T, Matsuda Y, Lienhard S, et al. Autocrine WNT signaling contributes to breast cancer cell proliferation via the canonical WNT pathway and EGFR transactivation[J]. Breast cancer research:BCR, 2007, 9:R63. doi:10.1186/bcr1769.
[75] DeAlmeida V I, Miao L, Ernst J A, et al. The soluble wnt receptor Frizzled8CRD-hFc inhibits the growth of teratocarcinomas in vivo[J]. Cancer Re-search, 2007, 67:5371-5379.
[76] Nagahata T, Shimada T, Harada A, et al. Amplification, up-regulation and over-expression of DVL-1, the human counterpart of the Drosophila disheveled gene, in primary breast cancers[J]. Cancer Science, 2003, 94:515-518.
[77] Prasad C P, Gupta S D, Rath G, et al. Wnt signaling pathway in invasive ductal carcinoma of the breast:Relationship between beta-catenin, dishevelled and cyclin D1 expression[J]. Oncology, 2007, 73:112-117.
[78] Dong Y, Cao B, Zhang M, et al. Epigenetic silencing of NKD2, a major component of Wnt signaling, promotes breast cancer growth[J]. Oncotarget, 2015, 6:22126-22138.
[79] Li C, Franklin J L, Graves-Deal R, et al. Myristoylated Naked2 escorts transforming growth factor alpha to the basolateral plasma membrane of polarized epithelial cells[J]. PNAS, 2004, 101:5571-5576.
[80] Yin X, Xiang T, Li L, et al. DACT1, an antagonist to Wnt/beta-catenin signaling, suppresses tumor cell growth and is frequently silenced in breast cancer[J]. Breast Cancer Research:BCR, 2013, 15:R23. doi:10.1186/bcr3399.
文章导航

/