Advanced Search
MA Lanjing, ZHANG Baihong. Recent Insights into Mechanisms Governing Breast Cancer Dormancy[J]. Cancer Research on Prevention and Treatment, 2023, 50(12): 1237-1242. DOI: 10.3971/j.issn.1000-8578.2023.23.0602
Citation: MA Lanjing, ZHANG Baihong. Recent Insights into Mechanisms Governing Breast Cancer Dormancy[J]. Cancer Research on Prevention and Treatment, 2023, 50(12): 1237-1242. DOI: 10.3971/j.issn.1000-8578.2023.23.0602

Recent Insights into Mechanisms Governing Breast Cancer Dormancy

Funding: 

Project of Gansu Provincial Youth Science and Technology Plan 22JR5RA021

More Information
  • Corresponding author:

    ZHANG Baihong, E-mail: bhzhang1999@126.com

  • Received Date: June 05, 2023
  • Revised Date: August 15, 2023
  • Available Online: January 12, 2024
  • Tumor dormancy refers to the status of disseminated cancer cells that remain in a viable yet not proliferating state for a prolonged period. Dormant cells will eventually "re-awake" resume their proliferation, and produce overt metastasis. The dormancy mechanism of cancer has attracted attention because of the close relationship between late recurrence and tumor dormancy. In this review, we illustrate the latest discoveries on the biological underpinnings of breast cancer dormancy and offer clinicians an overview of dormancy in breast cancer to guide them in the basic understanding of the complexity that underlies this process.

  • Competing interests: The authors declare that they have no competing interests.

  • [1]
    Hartkopf AD, Brucker SY, Taran FA, et al. Disseminated tumour cells from the bone marrow of early breast cancer patients: Results from an international pooled analysis[J]. Eur J Cancer, 2021, 154: 128-137. doi: 10.1016/j.ejca.2021.06.028
    [2]
    Summers MA, Mcdonald MM, Croucher PI. Cancer Cell Dormancy in Metastasis[J]. Cold Spring Harb Perspect Med, 2020, 10(4): a037556. doi: 10.1101/cshperspect.a037556
    [3]
    Blasco MT, Espuny I, Gomis RR. Ecology and evolution of dormant metastasis[J]. Trends Cancer, 2022, 8(7): 570-582. doi: 10.1016/j.trecan.2022.03.002
    [4]
    Tamamouna V, Pavlou E, Neophytou CM, et al. Regulation of Metastatic Tumor Dormancy and Emerging Opportunities for Therapeutic Intervention[J]. Int J Mol Sci, 2022, 23(22): 13931. doi: 10.3390/ijms232213931
    [5]
    Phan TG, Croucher PI. The dormant cancer cell life cycle[J]. Nat Rev Cancer, 2020, 20(7): 398-411. doi: 10.1038/s41568-020-0263-0
    [6]
    Elkholi IE, Lalonde A, Park M, et al. Breast Cancer Metastatic Dormancy and Relapse: An Enigma of Microenvironment(s)[J]. Cancer Res, 2022, 82(24): 4497-4510. doi: 10.1158/0008-5472.CAN-22-1902
    [7]
    Cufí S, Vazquez-Martin A, Oliveras-Ferraros C, et al. Autophagy positively regulates the CD44(+) CD24(-/low) breast cancer stem-like phenotype[J]. Cell Cycle, 2011, 10(22): 3871-3885. doi: 10.4161/cc.10.22.17976
    [8]
    Mowers EE, Sharifi MN, Macleod KF. Autophagy in cancer metastasis[J]. Oncogene, 2017, 36(12): 1619-1630. doi: 10.1038/onc.2016.333
    [9]
    Ovadia EM, Pradhan L, Sawicki LA, et al. Understanding ER+ Breast Cancer Dormancy Using Bioinspired Synthetic Matrices for Long-Term 3D Culture and Insights into Late Recurrence[J]. Adv Biosyst, 2020, 4(9): e2000119. doi: 10.1002/adbi.202000119
    [10]
    Vera-Ramirez L, Vodnala SK, Nini R, et al. Autophagy promotes the survival of dormant breast cancer cells and metastatic tumour recurrence[J]. Nat Commun, 2018, 9(1): 1944. doi: 10.1038/s41467-018-04070-6
    [11]
    Janji B, Viry E, Moussay E, et al. The multifaceted role of autophagy in tumor evasion from immune surveillance[J]. Oncotarget, 2016, 7(14): 17591-17607. doi: 10.18632/oncotarget.7540
    [12]
    Anlaş AA, Nelson CM. Soft Microenvironments Induce Chemoresistance by Increasing Autophagy Downstream of Integrin-Linked Kinase[J]. Cancer Res, 2020, 80(19): 4103-4113. doi: 10.1158/0008-5472.CAN-19-4021
    [13]
    Bildik G, Liang X, Sutton MN, et al. DIRAS3: An Imprinted Tumor Suppressor Gene that Regulates RAS and PI3K-driven Cancer Growth, Motility, Autophagy, and Tumor Dormancy[J]. Mol Cancer Ther, 2022, 21(1): 25-37. doi: 10.1158/1535-7163.MCT-21-0331
    [14]
    Aqbi HF, Tyutyunyk-Massey L, Keim RC, et al. Autophagy-deficient breast cancer shows early tumor recurrence and escape from dormancy[J]. Oncotarget, 2018, 9(31): 22113-22122. doi: 10.18632/oncotarget.25197
    [15]
    La Belle Flynn A, Calhoun BC, Sharma A, et al. Autophagy inhibition elicits emergence from metastatic dormancy by inducing and stabilizing Pfkfb3 expression[J]. Nature Commun, 2019, 10(1): 3668. doi: 10.1038/s41467-019-11640-9
    [16]
    Akkoc Y, Peker N, Akcay A, et al. Autophagy and Cancer Dormancy[J]. Front Oncol, 2021, 11: 627023. doi: 10.3389/fonc.2021.627023
    [17]
    Ruggieri L, Moretti A, Berardi R, et al. Host-Related Factors in the Interplay among Inflammation, Immunity and Dormancy in Breast Cancer Recurrence and Prognosis: An Overview for Clinicians[J]. Int J Mol Sci, 2023, 24(5): 4974. doi: 10.3390/ijms24054974
    [18]
    Phan TG, Croucher PI. The dormant cancer cell life cycle[J]. Nat Rev Cancer, 2020, 20(7): 398-411. doi: 10.1038/s41568-020-0263-0
    [19]
    Agudo J, Park ES, Rose SA, et al. Quiescent Tissue Stem Cells Evade Immune Surveillance[J]. Immunity, 2018, 48(2): 271-285. e275. doi: 10.1016/j.immuni.2018.02.001
    [20]
    Saudemont A, Quesnel B. In a model of tumor dormancy, long-term persistent leukemic cells have increased B7-H1 and B7.1 expression and resist CTL-mediated lysis[J]. Blood, 2004, 104(7): 2124-2133. doi: 10.1182/blood-2004-01-0064
    [21]
    Watt AC, Cejas P, Decristo MJ, et al. CDK4/6 inhibition reprograms the breast cancer enhancer landscape by stimulating AP-1 transcriptional activity[J]. Nat Cancer, 2021, 2(1): 34-48.
    [22]
    Pommier A, Anaparthy N, Memos N, et al. Unresolved endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases[J]. Science, 2018, 360(6394): eaao4908. doi: 10.1126/science.aao4908
    [23]
    Casanova-Acebes M, Dalla E, Leader AM, et al. Tissue-resident macrophages provide a pro-tumorigenic niche to early NSCLC cells[J]. Nature, 2021, 595(7868): 578-584. doi: 10.1038/s41586-021-03651-8
    [24]
    Bidwell BN, Slaney CY, Withana NP, et al. Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape[J]. Nat Med, 2012, 18(8): 1224-1231. doi: 10.1038/nm.2830
    [25]
    Lan Q, Peyvandi S, Duffey N, et al. Type I interferon/IRF7 axis instigates chemotherapy-induced immunological dormancy in breast cancer[J]. Oncogene, 2019, 38(15): 2814-2829. doi: 10.1038/s41388-018-0624-2
    [26]
    Bushnell GG, Deshmukh AP, Den Hollander P, et al. Breast cancer dormancy: need for clinically relevant models to address current gaps in knowledge[J]. NPJ Breast Cancer, 2021, 7(1): 66. doi: 10.1038/s41523-021-00269-x
    [27]
    De Cock JM, Shibue T, Dongre A, et al. Inflammation Triggers Zeb1-Dependent Escape from Tumor Latency[J]. Cancer Res, 2016, 76(23): 6778-6784. doi: 10.1158/0008-5472.CAN-16-0608
    [28]
    Tallón De Lara P, Castañón H, Vermeer M, et al. CD39+PD-1+CD8+ T cells mediate metastatic dormancy in breast cancer[J]. Nat Commun, 2021, 12(1): 769. doi: 10.1038/s41467-021-21045-2
    [29]
    Piranlioglu R, Lee E, Ouzounova M, et al. Primary tumor-induced immunity eradicates disseminated tumor cells in syngeneic mouse model[J]. Nature Commun, 2019, 10(1): 1430. doi: 10.1038/s41467-019-09015-1
    [30]
    Albrengues J, Shields MA, Ng D, et al. Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice[J]. Science, 2018, 361(6409): eaao4227. doi: 10.1126/science.aao4227
    [31]
    Barkan D, El Touny LH, Michalowski AM, et al. Metastatic Growth from Dormant Cells Induced by a Col-I–Enriched Fibrotic Environment[J]. Cancer Res, 2010, 70(14): 5706-5716. doi: 10.1158/0008-5472.CAN-09-2356
    [32]
    Walker ND, Elias M, Guiro K, et al. Exosomes from differentially activated macrophages influence dormancy or resurgence of breast cancer cells within bone marrow stroma[J]. Cell Death Dis, 2019, 10(2): 59. doi: 10.1038/s41419-019-1304-z
    [33]
    Correia AL, Guimaraes JC, Auf Der Maur P, et al. Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy[J]. Nature, 2021, 594(7864): 566-571. doi: 10.1038/s41586-021-03614-z
    [34]
    Shimizu H, Takeishi S, Nakatsumi H, et al. Prevention of cancer dormancy by Fbxw7 ablation eradicates disseminated tumor cells[J]. JCI Insight, 2019, 4(4): e125138. doi: 10.1172/jci.insight.125138
    [35]
    Ahn J, Lee JG, Chin C, et al. MSK1 functions as a transcriptional coactivator of p53 in the regulation of p21 gene expression[J]. Exp Mol Med, 2018, 50(10): 1-12.
    [36]
    Gawrzak S, Rinaldi L, Gregorio S, et al. MSK1 regulates luminal cell differentiation and metastatic dormancy in ER(+) breast cancer[J]. Nat Cell Biol, 2018, 20(2): 211-221. doi: 10.1038/s41556-017-0021-z
    [37]
    Zhang HS, Zhang ZG, Du GY, et al. Nrf2 promotes breast cancer cell migration via up-regulation of G6PD/HIF-1α/Notch1 axis[J]. J Cell Mol Med, 2019, 23(5): 3451-3463. doi: 10.1111/jcmm.14241
    [38]
    Fox DB, Garcia NMG, Mckinney BJ, et al. NRF2 activation promotes the recurrence of dormant tumour cells through regulation of redox and nucleotide metabolism[J]. Nat Metab, 2020, 2(4): 318-334. doi: 10.1038/s42255-020-0191-z
    [39]
    Bakhshandeh S, Werner C, Fratzl P, et al. Microenvironment-mediated cancer dormancy: Insights from metastability theory[J]. Proc Natl Acad Sci U S A, 2022, 119(1): e2111046118. doi: 10.1073/pnas.2111046118
    [40]
    Carcereri De Prati A, Butturini E, Rigo A, et al. Metastatic Breast Cancer Cells Enter Into Dormant State and Express Cancer Stem Cells Phenotype Under Chronic Hypoxia[J]. J Cell Biochem, 2017, 118(10): 3237-3248. doi: 10.1002/jcb.25972
    [41]
    Flynn AB, Schiemann WP. Autophagy in breast cancer metastatic dormancy: Tumor suppressing or tumor promoting functions?[J]. J Cancer Metastasis Treat, 2019, 5: 43.
    [42]
    Johnson RW, Finger EC, Olcina MM, et al. Induction of LIFR confers a dormancy phenotype in breast cancer cells disseminated to the bone marrow[J]. Nat Cell Biol, 2016, 18(10): 1078-1089. doi: 10.1038/ncb3408
    [43]
    Lee HR, Leslie F, Azarin SM. A facile in vitro platform to study cancer cell dormancy under hypoxic microenvironments using CoCl2[J]. J Biol Eng, 2018, 12: 12. doi: 10.1186/s13036-018-0106-7
    [44]
    Fang JY, Tan SJ, Wu YC, et al. From competency to dormancy: a 3D model to study cancer cells and drug responsiveness[J]. J Transl Med, 2016, 14: 38. doi: 10.1186/s12967-016-0798-8
    [45]
    Liu Y, Lv J, Liang X, et al. Fibrin Stiffness Mediates Dormancy of Tumor-Repopulating Cells via a Cdc42-Driven Tet2 Epigenetic Program[J]. Cancer Res, 2018, 78(14): 3926-3937. doi: 10.1158/0008-5472.CAN-17-3719
    [46]
    Pradhan S, Slater JH. Tunable hydrogels for controlling phenotypic cancer cell states to model breast cancer dormancy and reactivation[J]. Biomaterials, 2019, 215: 119177. doi: 10.1016/j.biomaterials.2019.04.022
    [47]
    Barney LE, Hall CL, Schwartz AD, et al. Tumor cell-organized fibronectin maintenance of a dormant breast cancer population[J]. Sci Adv, 2020, 6(11): eaaz4157. doi: 10.1126/sciadv.aaz4157
    [48]
    Montagner M, Bhome R, Hooper S, et al. Crosstalk with lung epithelial cells regulates Sfrp2-mediated latency in breast cancer dissemination[J]. Nat Cell Biol, 2020, 22(3): 289-296. doi: 10.1038/s41556-020-0474-3
    [49]
    Montagner M, Sahai E. In vitro Models of Breast Cancer Metastatic Dormancy[J]. Front Cell Dev Biol, 2020, 8: 37. doi: 10.3389/fcell.2020.00037
    [50]
    Ghajar CM, Peinado H, Mori H, et al. The perivascular niche regulates breast tumour dormancy[J]. Nat Cell Biol, 2013, 15(7): 807-817. doi: 10.1038/ncb2767
    [51]
    Carlson P, Dasgupta A, Grzelak CA, et al. Targeting the perivascular niche sensitizes disseminated tumour cells to chemotherapy[J]. Nat Cell Biol, 2019, 21(2): 238-250. doi: 10.1038/s41556-018-0267-0
    [52]
    Sandiford OA, Donnelly RJ, El-Far MH, et al. Mesenchymal Stem Cell-Secreted Extracellular Vesicles Instruct Stepwise Dedifferentiation of Breast Cancer Cells into Dormancy at the Bone Marrow Perivascular Region[J]. Cancer Res, 2021, 81(6): 1567-1582. doi: 10.1158/0008-5472.CAN-20-2434
    [53]
    Schmittnaegel M, Rigamonti N, Kadioglu E, et al. Dual angiopoietin-2 and VEGFA inhibition elicits antitumor immunity that is enhanced by PD-1 checkpoint blockade[J]. Sci Transl Med, 2017, 9(385): eaak9670. doi: 10.1126/scitranslmed.aak9670
    [54]
    Hughes R, Chen X, Cowley N, et al. Osteoblast-Derived Paracrine and Juxtacrine Signals Protect Disseminated Breast Cancer Cells from Stress[J]. Cancers (Basel), 2021, 13(6): 1366. doi: 10.3390/cancers13061366
    [55]
    Kolb AD, Shupp AB, Mukhopadhyay D, et al. Osteoblasts are "educated" by crosstalk with metastatic breast cancer cells in the bone tumor microenvironment[J]. Breast Cancer Res, 2019, 21(1): 31. doi: 10.1186/s13058-019-1117-0
    [56]
    Shupp AB, Neupane M, Agostini LC, et al. Stromal-Derived Extracellular Vesicles Suppress Proliferation of Bone Metastatic Cancer Cells Mediated by ERK2[J]. Mol Cancer Res, 2021, 19(10): 1763-1777. doi: 10.1158/1541-7786.MCR-20-0981
    [57]
    Nobre AR, Risson E, Singh DK, et al. Bone marrow NG2+/Nestin+ mesenchymal stem cells drive DTC dormancy via TGF-β2[J]. Nat Cancer, 2021, 2(3): 327-339. doi: 10.1038/s43018-021-00179-8
    [58]
    Melzer C, Von Der Ohe J, Luo T, et al. Spontaneous Fusion of MSC with Breast Cancer Cells Can Generate Tumor Dormancy[J]. Int J Mol Sci, 2021, 22(11): 5930. doi: 10.3390/ijms22115930
    [59]
    Bartosh TJ, Ullah M, Zeitouni S, et al. Cancer cells enter dormancy after cannibalizing mesenchymal stem/stromal cells (MSCs)[J]. Proc Natl Acad Sci U S A, 2016, 113(42): E6447-E6456.
    [60]
    Tivari S, Lu H, Dasgupta T, et al. Reawakening of dormant estrogen-dependent human breast cancer cells by bone marrow stroma secretory senescence[J]. Cell Commun Signal, 2018, 16(1): 48. doi: 10.1186/s12964-018-0259-5
    [61]
    Liu Y, Zhang P, Wu Q, et al. Long non-coding RNA NR2F1-AS1 induces breast cancer lung metastatic dormancy by regulating NR2F1 and ΔNp63[J]. Nature Commun, 2021, 12(1): 5232. doi: 10.1038/s41467-021-25552-0
    [62]
    Abdalla MOA, Yamamoto T, Maehara K, et al. The Eleanor ncRNAs activate the topological domain of the ESR1 locus to balance against apoptosis[J]. Nature Commun, 2019, 10(1): 3778. doi: 10.1038/s41467-019-11378-4
    [63]
    Fukuoka M, Ichikawa Y, Osako T, et al. The ELEANOR noncoding RNA expression contributes to cancer dormancy and predicts late recurrence of estrogen receptor-positive breast cancer[J]. Cancer Sci, 2022, 113(7): 2336-2351. doi: 10.1111/cas.15373
    [64]
    Kumar D, Gurrapu S, Han H, et al. Malat1 lncRNA controls metastatic reactivation of dormant breast cancer by immune evasion[J]. J Immunother Cancer, 2020, 8: A450-A451.
    [65]
    Papadaki C, Stratigos M, Markakis G, et al. Circulating microRNAs in the early prediction of disease recurrence in primary breast cancer[J]. Breast Cancer Research, 2018, 20(1): 72. doi: 10.1186/s13058-018-1001-3
  • Related Articles

    [1]FU Yuting, YANG Wenjun, JIANG Binyuan. Advances of Non-coding RNA in Oral Cancer[J]. Cancer Research on Prevention and Treatment, 2022, 49(12): 1296-1301. DOI: 10.3971/j.issn.1000-8578.2022.22.0498
    [2]GUO Xin, DU Hua, SHI Yingxu. Exosomal Delivery of Non-coding RNA Regulates Breast Bancer Drug Resistance[J]. Cancer Research on Prevention and Treatment, 2022, 49(10): 1071-1076. DOI: 10.3971/j.issn.1000-8578.2022.22.0142
    [3]SU Jiaqing, LI Zhiwei, WAN Zhaojuan, WANG Fanghua, WANG Meng, ZHANG Hengyang, ZHANG Huixin, ZHOU Bailing. Expression of Four Long Non-coding RNAs in Breast Cancer and Their Relation with Patient's Prognosis[J]. Cancer Research on Prevention and Treatment, 2020, 47(2): 90-96. DOI: 10.3971/j.issn.1000-8578.2020.19.0617
    [4]HOU Chan, WEI Hailiang, LI Jingtao, YAN Shuguang, ZHOU Jun. Advances in Non-coding RNA Regulating Kupffer Cell Polarization in Intervention of Malignant Transformation of Precancerous Lesions of Liver[J]. Cancer Research on Prevention and Treatment, 2019, 46(9): 851-855. DOI: 10.3971/j.issn.1000-8578.2019.19.0171
    [5]SONG Peng, LONG Tong, LIANG Peiyu, OU Shanji. Effects of Long Non-coding RNA-MALAT1 on Proliferation and Apoptosis of Prostate Cancer Cells[J]. Cancer Research on Prevention and Treatment, 2019, 46(5): 411-416. DOI: 10.3971/j.issn.1000-8578.2019.18.1198
    [6]CHEN Mengxue, LI Xueliang. Research Progress of Long Non-coding RNA in Esophageal Cancer[J]. Cancer Research on Prevention and Treatment, 2018, 45(11): 932-935. DOI: 10.3971/j.issn.1000-8578.2018.18.0399
    [7]FENG Shuidong, ZHU Zemei, YANG Sisi, HE Jianqin, ZHANG Kaifang, YANG Jihua, LING Hongyan. Effect of Long Non-coding RNA LOC100294362 on Proliferation and Invasion of Breast Cancer Cells[J]. Cancer Research on Prevention and Treatment, 2016, 43(5): 366-370. DOI: 10.3971/j.issn.1000-8578.2016.05.010
    [8]LUO Yanhong, LIN Juanjuan, WANG Kai, KONG Danli, HE Yuqing. Association Between Long Non-coding RNA and Cervical Cancer[J]. Cancer Research on Prevention and Treatment, 2016, 43(1): 82-86. DOI: 10.3971/j.issn.1000-8578.2016.01.018
    [9]ZHANG Xinli, ZHAO Yanhua, LI Shu'na, ZHANG Wenling. Screening of Long Non-coding RNA in Colon Cancer by Bioinformatics[J]. Cancer Research on Prevention and Treatment, 2015, 42(05): 446-449. DOI: 10.3971/j.issn.1000-8578.2015.05.005
    [10]YANG Qingqing, DENG Yanfei. Expression of Specific Long Non-coding RNA in Nasopharyngeal Carcinoma and Related Significance[J]. Cancer Research on Prevention and Treatment, 2015, 42(03): 219-224. DOI: 10.3971/j.issn.1000-8578.2015.03.002
  • Cited by

    Periodical cited type(5)

    1. 苗凌肖, 赵金叶, 李恒, 单凤姣, 张翠红. CBCT图像引导下负压气垫和热塑体膜在腹盆腔肿瘤放疗中的摆位误差比较及体质量指数对复位通过率的影响. 医疗卫生装备. 2025(07)
    2. 王建林,张天,张文君,胡强. 基于机械性能检测分析VitalBeam型直线加速器输出剂量的稳定性评估及故障案例分析. 中国医学装备. 2024(06): 209-213 .
    3. 赵亮,马超,闵骁,熊兵,吴炎,杨爱民. 基于锥形束CT研究不同部位计划靶区外放边界. 现代肿瘤医学. 2024(18): 3549-3555 .
    4. 周军,李寒旭,黄志兵,万久庆,李东春,钟良志. CBCT和EXT图像引导系统在高级别脑胶质瘤放疗中的应用分析. 医疗卫生装备. 2024(08): 57-62 .
    5. 陈文强,赵军军,李扬,袁慧杰. 对比和分析腹部肿瘤影像引导放疗中千伏级锥形束CT与兆伏级电子摄像系统的应用效果. 影像研究与医学应用. 2024(23): 181-183 .

    Other cited types(0)

Catalog

    Article views (2440) PDF downloads (1013) Cited by(5)

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return