Tumor Metastasis: Molecular Insights and Evolving Paradigms

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2011 Oct 18

PMID 22000009

Citations 1901

Authors

Scott Valastyan

Robert A Weinberg

Affiliations

Soon will be listed here.

Abstract

Metastases represent the end products of a multistep cell-biological process termed the invasion-metastasis cascade, which involves dissemination of cancer cells to anatomically distant organ sites and their subsequent adaptation to foreign tissue microenvironments. Each of these events is driven by the acquisition of genetic and/or epigenetic alterations within tumor cells and the co-option of nonneoplastic stromal cells, which together endow incipient metastatic cells with traits needed to generate macroscopic metastases. Recent advances provide provocative insights into these cell-biological and molecular changes, which have implications regarding the steps of the invasion-metastasis cascade that appear amenable to therapeutic targeting.

Citing Articles

Biomimetic Self-Oxygenated Immunoliposome for Cancer-Targeted Photodynamic Immunotherapy.

Tang Y, Tang T, Li Y, Wu J, Liu X, Xiang D Int J Nanomedicine. 2025; 20:2743-2759.

PMID: 40066322 PMC: 11892501. DOI: 10.2147/IJN.S508696.

Extraction of a stromal metastatic gene signature in breast cancer via spatial profiling.

Bertolazzi G, Cancila V, Vacca D, Belmonte B, Lecis D, Moghaddam P J Exp Clin Cancer Res. 2025; 44(1):89.

PMID: 40065328 PMC: 11892262. DOI: 10.1186/s13046-025-03353-3.

Establishing a cryopreserved biobank of living tumor tissues for drug sensitivity testing.

Chen P, Zhou J, Chu X, Feng Y, Zeng Q, Lei J Bioact Mater. 2025; 46:582-596.

PMID: 40061435 PMC: 11889390. DOI: 10.1016/j.bioactmat.2024.09.008.

Modulating lipid metabolism by nanoparticles (NPs)-mediated ACSL3 silencing to inhibit hepatocellular carcinoma growth and metastasis.

Huang L, Xu R, Chen S, Lin C, Li W, Li S Mol Cancer. 2025; 24(1):73.

PMID: 40059153 PMC: 11892139. DOI: 10.1186/s12943-025-02274-1.

ATXN3 deubiquitinates ZEB1 and facilitates epithelial-mesenchymal transition in glioblastoma.

Wei R, Shi X, Qiu W, Yang M, Chen Y, Song S Sci Rep. 2025; 15(1):7868.

PMID: 40050358 PMC: 11885642. DOI: 10.1038/s41598-025-92317-w.

References

Kouros-Mehr H, Bechis S, Slorach E, Littlepage L, Egeblad M, Ewald A . GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model. Cancer Cell. 2008; 13(2):141-52. PMC: 2262951. DOI: 10.1016/j.ccr.2008.01.011. View

Gocheva V, Wang H, Gadea B, Shree T, Hunter K, Garfall A . IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev. 2010; 24(3):241-55. PMC: 2811826. DOI: 10.1101/gad.1874010. View

Navin N, Kendall J, Troge J, Andrews P, Rodgers L, McIndoo J . Tumour evolution inferred by single-cell sequencing. Nature. 2011; 472(7341):90-4. PMC: 4504184. DOI: 10.1038/nature09807. View

Grivennikov S, Greten F, Karin M . Immunity, inflammation, and cancer. Cell. 2010; 140(6):883-99. PMC: 2866629. DOI: 10.1016/j.cell.2010.01.025. View

Campbell P, Yachida S, Mudie L, Stephens P, Pleasance E, Stebbings L . The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature. 2010; 467(7319):1109-13. PMC: 3137369. DOI: 10.1038/nature09460. View

Weis S, Cui J, Barnes L, Cheresh D . Endothelial barrier disruption by VEGF-mediated Src activity potentiates tumor cell extravasation and metastasis. J Cell Biol. 2004; 167(2):223-9. PMC: 2172541. DOI: 10.1083/jcb.200408130. View

Cristofanilli M, Budd G, Ellis M, Stopeck A, Matera J, Miller M . Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med. 2004; 351(8):781-91. DOI: 10.1056/NEJMoa040766. View

Levental K, Yu H, Kass L, Lakins J, Egeblad M, Erler J . Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell. 2009; 139(5):891-906. PMC: 2788004. DOI: 10.1016/j.cell.2009.10.027. View

Aguirre-Ghiso J . Models, mechanisms and clinical evidence for cancer dormancy. Nat Rev Cancer. 2007; 7(11):834-46. PMC: 2519109. DOI: 10.1038/nrc2256. View

10.

Paik S, Shak S, Tang G, Kim C, Baker J, Cronin M . A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004; 351(27):2817-26. DOI: 10.1056/NEJMoa041588. View

11.

Gupta G, Perk J, Acharyya S, de Candia P, Mittal V, Todorova-Manova K . ID genes mediate tumor reinitiation during breast cancer lung metastasis. Proc Natl Acad Sci U S A. 2007; 104(49):19506-11. PMC: 2148319. DOI: 10.1073/pnas.0709185104. View

12.

Yu S, Chen H, Chang G, Chen C, Chen H, Singh S . MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell. 2008; 13(1):48-57. DOI: 10.1016/j.ccr.2007.12.008. View

13.

Gilbert L, Hemann M . DNA damage-mediated induction of a chemoresistant niche. Cell. 2010; 143(3):355-66. PMC: 2972353. DOI: 10.1016/j.cell.2010.09.043. View

14.

Mazzieri R, Pucci F, Moi D, Zonari E, Ranghetti A, Berti A . Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells. Cancer Cell. 2011; 19(4):512-26. DOI: 10.1016/j.ccr.2011.02.005. View

15.

Ebos J, Lee C, Cruz-Munoz W, Bjarnason G, Christensen J, Kerbel R . Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell. 2009; 15(3):232-9. PMC: 4540346. DOI: 10.1016/j.ccr.2009.01.021. View

16.

Fan C, Oh D, Wessels L, Weigelt B, Nuyten D, Nobel A . Concordance among gene-expression-based predictors for breast cancer. N Engl J Med. 2006; 355(6):560-9. DOI: 10.1056/NEJMoa052933. View

17.

Oskarsson T, Nagorny P, Krauss I, Perez L, Mandal M, Yang G . Diverted total synthesis leads to the generation of promising cell-migration inhibitors for treatment of tumor metastasis: in vivo and mechanistic studies on the migrastatin core ether analog. J Am Chem Soc. 2010; 132(9):3224-8. PMC: 2863049. DOI: 10.1021/ja9101503. View

18.

Brown D, Ruoslahti E . Metadherin, a cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell. 2004; 5(4):365-74. DOI: 10.1016/s1535-6108(04)00079-0. View

19.

McAllister S, Gifford A, Greiner A, Kelleher S, Saelzler M, Ince T . Systemic endocrine instigation of indolent tumor growth requires osteopontin. Cell. 2008; 133(6):994-1005. PMC: 4121664. DOI: 10.1016/j.cell.2008.04.045. View

20.

Carmeliet P, Jain R . Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat Rev Drug Discov. 2011; 10(6):417-27. DOI: 10.1038/nrd3455. View