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Metastatic breast tumors express increased tau, which promotes microtentacle formation and the reattachment of detached breast tumor cells


The cytoskeletal organization of detached and circulating tumor cells (CTCs) is currently not well defined and may provide potential targets for new therapies to limit metastatic tumor spread. In vivo, CTCs reattach in distant tissues by a mechanism that is tubulin-dependent and suppressed by polymerized actin. The cytoskeletal mechanisms that promote reattachment of CTCs match exactly with the mechanisms supporting tubulin microtentacles (McTN), which we have recently identified in detached breast tumor cells. In this study, we aimed to investigate how McTN formation is affected by the microtubule-associated protein, tau, which is expressed in a subset of chemotherapy-resistant breast cancers. We demonstrate that endogenous tau protein localizes to McTNs and is both necessary and sufficient to promote McTN extension in detached breast tumor cells. Tau-induced McTNs increase reattachment of suspended cells and retention of CTCs in lung capillaries. Analysis of patient-matched primary and metastatic tumors reveals that 52% possess tau expression in metastases and 26% display significantly increased tau expression over disease progression. Tau enrichment in metastatic tumors and the ability of tau to promote tumor cell reattachment through McTN formation support a model in which tau-induced microtubule stabilization provides a selective advantage during tumor metastasis.

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circulating tumor cell


extracellular matrix




microtubule-associated protein




non-silencing control




tissue microarray


vehicle control


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This study was supported by Grant R01-CA124704 from National Cancer Institute, Breast Cancer Idea Award from USA Medical Research and Materiel Command (BC061047) and a Clinical Innovator Award from Flight Attendants Medical Research Institute (CIA-062497). We thank Dr I-Chu Tseng and the Dr Chen-Yong Lin laboratory for immunohistochemistry assistance, Dr Larry Changwan Lu for his assistance with the statistical analyses, Aric Colunga and the Dr Laure Aurelian laboratory for imaging assistance, Dr William Twaddell for assistance with pathological scoring of vimentin staining, and Dr Michele Weiss for Figure 6 assistance.

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Correspondence to S S Martin.

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Matrone, M., Whipple, R., Thompson, K. et al. Metastatic breast tumors express increased tau, which promotes microtentacle formation and the reattachment of detached breast tumor cells. Oncogene 29, 3217–3227 (2010).

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  • microtentacles
  • tau
  • microtubule-associated proteins
  • microtubules
  • circulating tumor cells

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