Schwartz RS, Erban JK. Timing of metastasis in breast cancer. N Engl J Med. 2017;376:2486–8.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144:646–74.
Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V. Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer. 2007;109:1721–8.
Bianchini G, Balko JM, Mayer IA, Sanders ME, Gianni L. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease. Nat Rev Clin Oncol. 2016;13:674–90.
Langley RR, Fidler IJ. The seed and soil hypothesis revisited–the role of tumor-stroma interactions in metastasis to different organs. Int J Cancer. 2011;128:2527–35.
O’Brien K, Rani S, Corcoran C, Wallace R, Hughes L, Friel AM, et al. Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells. Eur J Cancer. 2013;49:1845–59.
Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, et al. Tumour exosome integrins determine organotropic metastasis. Nature. 2015;527:329–35.
Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem. 1987;262:9412–20.
Colombo M, Raposo G, Théry C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30:255–89.
Schlange T, Matsuda Y, Lienhard S, Huber A, Hynes NE. Autocrine WNT signaling contributes to breast cancer cell proliferation via the canonical WNT pathway and EGFR transactivation. Breast Cancer Res. 2007;9:R63.
Li Y, Jin K, van Pelt GW, van Dam H, Yu X, Mesker WE, et al. c-Myb enhances breast cancer invasion and metastasis through the Wnt/β-Catenin/Axin2 pathway. Cancer Res. 2016;76:3364–75.
Wang X, Jung YS, Jun S, Lee S, Wang W, Schneider A, et al. PAF-Wnt signaling-induced cell plasticity is required for maintenance of breast cancer cell stemness. Nat Commun. 2016;7:10633.
Wellenstein MD, Coffelt SB, Duits DEM, van Miltenburg MH, Slagter M, de Rink I, et al. Loss of p53 triggers WNT-dependent systemic inflammation to drive breast cancer metastasis. Nature. 2019;572:538–42.
Nusse R, Varmus HE. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell. 1982;31:99–109.
Pohl SG, Brook N, Agostino M, Arfuso F, Kumar AP, Dharmarajan A. Wnt signaling in triple-negative breast cancer. Oncogenesis. 2017;6: e310.
Koles K, Budnik V. Exosomes go with the Wnt. Cell Logist. 2012;2:169–73.
Gross JC, Chaudhary V, Bartscherer K, Boutros M. Active Wnt proteins are secreted on exosomes. Nat Cell Biol. 2012;14:1036–45.
Dexter DL, Kowalski HM, Blazar BA, Fligiel Z, Vogel R, Heppner GH. Heterogeneity of tumor cells from a single mouse mammary tumor. Cancer Res. 1978;38:3174–81.
Aslakson CJ, Miller FR. Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor. Cancer Res. 1992;52:1399–405.
Wagenblast E, Soto M, Gutiérrez-Ángel S, Hartl CA, Gable AL, Maceli AR, et al. A model of breast cancer heterogeneity reveals vascular mimicry as a driver of metastasis. Nature. 2015;520:358–62.
Tamura M, Sugiura S, Takagi T, Satoh T, Sumaru K, Kanamori T, et al. Morphology-based optical separation of subpopulations from a heterogeneous murine breast cancer cell line. PLoS ONE. 2017;12: e0179372.
Lasso P, Llano Murcia M, Sandoval TA, Urueña C, Barreto A, Fiorentino S. Breast tumor cells highly resistant to drugs are controlled only by the immune response induced in an immunocompetent mouse model. Integr Cancer Ther. 2019;18:1534735419848047.
Yoshimura T, Nakamura K, Li C, Fujisawa M, Shiina T, Imamura M, et al. Cancer cell-derived granulocyte-macrophage colony-stimulating factor is dispensable for the progression of 4T1 murine breast cancer. Int J Mol Sci. 2019;20:E6342.
Sakaguchi M, Watanabe M, Kinoshita R, Kaku H, Ueki H, Futami J, et al. Dramatic increase in expression of a transgene by insertion of promoters downstream of the cargo gene. Mol Biotechnol. 2014;56:621–30.
Mahi NA, Najafabadi MF, Pilarczyk M, Kouril M, Medvedovic M. GREIN: an interactive web platform for re-analyzing GEO RNA-seq data. Sci Rep. 2019;9:7580.
Lánczky A, Győrffy B. Web-based survival analysis tool tailored for medical research (KMplot): development and implementation. J Med Internet Res. 2021;23: e27633.
Bielecka ZF, Maliszewska-Olejniczak K, Safir IJ, Szczylik C, Czarnecka AM. Three-dimensional cell culture model utilization in cancer stem cell research. Biol Rev Camb Philos Soc. 2017;92:1505–20.
Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F, et al. Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science. 2008;319:1244–7.
Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol. 2010;12:19–30.
Bikkavilli RK, Avasarala S, Van Scoyk M, Arcaroli J, Brzezinski C, Zhang W, et al. Wnt7a is a novel inducer of β-catenin-independent tumor-suppressive cellular senescence in lung cancer. Oncogene. 2015;34:5317–28.
Huang X, Zhu H, Gao Z, Li J, Zhuang J, Dong Y, et al. Wnt7a activates canonical Wnt signaling, promotes bladder cancer cell invasion, and is suppressed by miR-370-3p. J Biol Chem. 2018;293:6693–706.
Lan L, Wang W, Huang Y, Bu X, Zhao C. Roles of Wnt7a in embryo development, tissue homeostasis, and human diseases. J Cell Biochem. 2019;120:18588–98.
Le Grand F, Jones AE, Seale V, Scimè A, Rudnicki MA. Wnt7a activates the planar cell polarity pathway to drive the symmetric expansion of satellite stem cells. Cell Stem Cell. 2009;4:535–47.
Ai P, Xu X, Xu S, Wei Z, Tan S, Li J. Overexpression of Wnt7a enhances radiosensitivity of non-small-cell lung cancer via the Wnt/JNK pathway. Biol Open. 2020;9:bio050575.
Xie H, Ma Y, Li J, Chen H, Xie Y, Chen M, et al. WNT7A promotes EGF-induced migration of oral squamous cell carcinoma cells by activating β-catenin/MMP9-mediated signaling. Front Pharmacol. 2020;11:98.
von Maltzahn J, Bentzinger CF, Rudnicki MA. Wnt7a-Fzd7 signalling directly activates the Akt/mTOR anabolic growth pathway in skeletal muscle. Nat Cell Biol. 2011;14:186–91.
Yoshioka S, King ML, Ran S, Okuda H, MacLean JA, McAsey ME, et al. WNT7A regulates tumor growth and progression in ovarian cancer through the WNT/β-catenin pathway. Mol Cancer Res. 2012;10:469–82.
Xu J, Prosperi JR, Choudhury N, Olopade OI, Goss KH. β-Catenin is required for the tumorigenic behavior of triple-negative breast cancer cells. PLoS ONE. 2015;10: e0117097.
Mohammed MK, Shao C, Wang J, Wei Q, Wang X, Collier Z, et al. Wnt/β-catenin signaling plays an ever-expanding role in stem cell self-renewal, tumorigenesis and cancer chemoresistance. Genes Dis. 2016;3:11–40.
Ganesh K, Massagué J. Targeting metastatic cancer. Nat Med. 2021;27:34–44.
Katoh M. Canonical and non-canonical WNT signaling in cancer stem cells and their niches: cellular heterogeneity, omics reprogramming, targeted therapy and tumor plasticity (review). Int J Oncol. 2017;51:1357–69.
Yin S, Cheryan VT, Xu L, Rishi AK, Reddy KB. Myc mediates cancer stem-like cells and EMT changes in triple negative breast cancers cells. PLoS ONE. 2017;12: e0183578.
Zhang F, Li K, Yao X, Wang H, Li W, Wu J, et al. A miR-567-PIK3AP1-PI3K/AKT-c-Myc feedback loop regulates tumour growth and chemoresistance in gastric cancer. EBioMedicine. 2019;44:311–21.
Avgustinova A, Iravani M, Robertson D, Fearns A, Gao Q, Klingbeil P, et al. Tumour cell-derived Wnt7a recruits and activates fibroblasts to promote tumour aggressiveness. Nat Commun. 2016;7:10305.
Liu T, Han C, Wang S, Fang P, Ma Z, Xu L, et al. Cancer-associated fibroblasts: an emerging target of anti-cancer immunotherapy. J Hematol Oncol. 2019;12:86.
Vermeulen L, De Sousa E Melo F, van der Heijden M, Cameron K, de Jong JH, Borovski T, et al. Wnt activity defines colon cancer stem cells and is regulated by the microenvironment. Nat Cell Biol. 2010;12:468–76.
Tang Y, Nakada MT, Rafferty P, Laraio J, McCabe FL, Millar H, Cunningham M, Snyder LA, Bugelski P, Yan L. Regulation of vascular endothelial growth factor expression by EMMPRIN via the PI3K-Akt signaling pathway. Mol Cancer Res. 2006;4:371–8.
Andor N, Graham TA, Jansen M, Xia LC, Aktipis CA, Petritsch C, et al. Pan-cancer analysis of the extent and consequences of intratumor heterogeneity. Nat Med. 2016;22:105–13.
Wang Y, Waters J, Leung ML, Unruh A, Roh W, Shi X, et al. Clonal evolution in breast cancer revealed by single nucleus genome sequencing. Nature. 2014;512:155–60.
Skibinski A, Kuperwasser C. The origin of breast tumor heterogeneity. Oncogene. 2015;34:5309–16.
Yang B, Feng X, Liu H, Tong R, Wu J, Li C, et al. High-metastatic cancer cells derived exosomal miR92a-3p promotes epithelial-mesenchymal transition and metastasis of low-metastatic cancer cells by regulating PTEN/Akt pathway in hepatocellular carcinoma. Oncogene. 2020;39:6529–43.
Sun H, Wang C, Hu B, Gao X, Zou T, Luo Q, et al. Exosomal S100A4 derived from highly metastatic hepatocellular carcinoma cells promotes metastasis by activating STAT3. Signal Transduct Target Ther. 2021;6:187.
Shen S, Song Y, Zhao B, Xu Y, Ren X, Zhou Y, et al. Cancer-derived exosomal miR-7641 promotes breast cancer progression and metastasis. Cell Commun Signal. 2021;19:20.
Massagué J, Obenauf AC. Metastatic colonization by circulating tumour cells. Nature. 2016;529:298–306.
Xiang X, Deng Z, Zhuang X, Ju S, Mu J, Jiang H, et al. Grhl2 determines the epithelial phenotype of breast cancers and promotes tumor progression. PLoS ONE. 2012;7: e50781.
Kröger C, Afeyan A, Mraz J, Eaton EN, Reinhardt F, Khodor YL, et al. Acquisition of a hybrid E/M state is essential for tumorigenicity of basal breast cancer cells. Proc Natl Acad Sci USA. 2019;116:7353–62.
Cleary AS, Leonard TL, Gestl SA, Gunther EJ. Tumour cell heterogeneity maintained by cooperating subclones in Wnt-driven mammary cancers. Nature. 2014;508:113–7.
Tkach M, Théry C. Communication by extracellular vesicles: where we are and where we need to go. Cell. 2016;164:1226–32.
Kowal J, Arras G, Colombo M, Jouve M, Morath JP, Primdal-Bengtson B, et al. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc Natl Acad Sci USA. 2016;113:E968–77.
Syn N, Wang L, Sethi G, Thiery JP, Goh BC. Exosome-mediated metastasis: from epithelial-mesenchymal transition to escape from immunosurveillance. Trends Pharmacol Sci. 2016;37:606–17.
Yang J, Nie J, Ma X, Wei Y, Peng Y, Wei X. Targeting PI3K in cancer: mechanisms and advances in clinical trials. Mol Cancer. 2019;18:26.
Chung J, Kuo CJ, Crabtree GR, Blenis J. Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases. Cell. 1992;69:1227–36.
Klos KS, Wyszomierski SL, Sun M, Tan M, Zhou X, Li P, et al. ErbB2 increases vascular endothelial growth factor protein synthesis via activation of mammalian target of rapamycin/p70S6K leading to increased angiogenesis and spontaneous metastasis of human breast cancer cells. Cancer Res. 2006;66:2028–37.
Akar U, Ozpolat B, Mehta K, Lopez-Berestein G, Zhang D, Ueno NT, et al. Targeting p70S6K prevented lung metastasis in a breast cancer xenograft model. Mol Cancer Ther. 2010;9:1180–7.
Bärlund M, Forozan F, Kononen J, Bubendorf L, Chen Y, Bittner ML, et al. Detecting activation of ribosomal protein S6 kinase by complementary DNA and tissue microarray analysis. J Natl Cancer Inst. 2000;92:1252–9.
Foster DA, Toschi A. Targeting mTOR with rapamycin: one dose does not fit all. Cell Cycle. 2009;8:1026–9.
Sarbassov DD, Ali SM, Sengupta S, Sheen JH, Hsu PP, Bagley AF, et al. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell. 2006;22:159–68.
Song S, Huang H, Guan X, Fiesler V, Bhuiyan MIH, Liu R, et al. Activation of endothelial Wnt/β-catenin signaling by protective astrocytes repairs BBB damage in ischemic stroke. Prog Neurobiol. 2021;199: 101963.
Varley KE, Gertz J, Roberts BS, Davis NS, Bowling KM, Kirby MK, et al. Recurrent read-through fusion transcripts in breast cancer. Breast Cancer Res Treat. 2014;146:287–97.
Perou CM. Molecular stratification of triple-negative breast cancers. Oncologist. 2011;16(suppl 1):61–70.