American Association for Cancer Research
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Supplementary Figure S3 from Tumor Cell–Driven Extracellular Matrix Remodeling Drives Haptotaxis during Metastatic Progression

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journal contribution
posted on 2023-04-03, 21:04 authored by Madeleine J. Oudin, Oliver Jonas, Tatsiana Kosciuk, Liliane C. Broye, Bruna C. Guido, Jeff Wyckoff, Daisy Riquelme, John M. Lamar, Sreeja B. Asokan, Charlie Whittaker, Duanduan Ma, Robert Langer, Michael J. Cima, Kari B. Wisinski, Richard O. Hynes, Douglas A. Lauffenburger, Patricia J. Keely, James E. Bear, Frank B. Gertler

Supplementary Figure S3. TCGA analysis supplementary analysis and characterization of MenaINV-specific monoclonal antibody.


Breast Cancer Research Foundation

Ludwig Center at MIT


Howard Hughes Medical Institute


Kathy and Curt Marble Cancer Research

Prostate Cancer Foundation




Fibronectin (FN) is a major component of the tumor microenvironment, but its role in promoting metastasis is incompletely understood. Here, we show that FN gradients elicit directional movement of breast cancer cells, in vitro and in vivo. Haptotaxis on FN gradients requires direct interaction between α5β1 integrin and MENA, an actin regulator, and involves increases in focal complex signaling and tumor cell–mediated extracellular matrix (ECM) remodeling. Compared with MENA, higher levels of the prometastatic MENAINV isoform associate with α5, which enables 3-D haptotaxis of tumor cells toward the high FN concentrations typically present in perivascular space and in the periphery of breast tumor tissue. MENAINV and FN levels were correlated in two breast cancer cohorts, and high levels of MENAINV were significantly associated with increased tumor recurrence as well as decreased patient survival. Our results identify a novel tumor cell–intrinsic mechanism that promotes metastasis through ECM remodeling and ECM-guided directional migration.Significance: Here, we provide new insight into how tumor cell:ECM interactions generate signals and structures that promote directed tumor cell migration, a critical component of metastasis. Our results identify a tumor cell–intrinsic mechanism driven by the actin regulatory protein MENA that promotes ECM remodeling and haptotaxis along FN gradients. Cancer Discov; 6(5); 516–31. ©2016 AACR.See related commentary by Santiago-Medina and Yang, p. 474.This article is highlighted in the In This Issue feature, p. 461