Microenvironment rigidity modulates responses to the HER2 receptor tyrosine kinase inhibitor lapatinib via YAP and TAZ transcription factors

The relative contributions of the molecular and physical characteristics of tissue microenvironments to cell responses to receptor tyrosine kinase inhibitors are not well understood. Polymer-based tissue culture substrata were used to isolate and study the contribution of matrix elastic modulus. YAP and TAZ, transcriptional coactivators and mechanotransducers of the Hippo pathway, are essential for mediating elastic modulus–dependent resistance to the HER2-targeted anticancer drug, lapatinib.

[1]  Shelly R. Peyton,et al.  Sorafenib resistance and JNK signaling in carcinoma during extracellular matrix stiffening. , 2014, Biomaterials.

[2]  Vladimir B Bajic,et al.  Classifying the estrogen receptor status of breast cancers by expression profiles reveals a poor prognosis subpopulation exhibiting high expression of the ERBB2 receptor. , 2003, Human molecular genetics.

[3]  A. Martin,et al.  Assessment of epidermal growth factor receptor (EGFR, ErbB1) and HER2 (ErbB2) protein expression levels and response to lapatinib (Tykerb®, GW572016) in an expanded panel of human normal and tumour cell lines , 2007, Cell proliferation.

[4]  C. Mein,et al.  Yes-associated protein (YAP) functions as a tumor suppressor in breast , 2008, Cell Death and Differentiation.

[5]  Joe W. Gray,et al.  HER2 signaling pathway activation and response of breast cancer cells to HER2-targeting agents is dependent strongly on the 3D microenvironment , 2010, Breast Cancer Research and Treatment.

[6]  Joel Greshock,et al.  Novel mechanism of lapatinib resistance in HER2-positive breast tumor cells: activation of AXL. , 2009, Cancer research.

[7]  Daniel Benten,et al.  Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cells , 2011, Hepatology.

[8]  Wen-Lin Kuo,et al.  A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. , 2006, Cancer cell.

[9]  R. Hynes,et al.  The Hippo pathway target, YAP, promotes metastasis through its TEAD-interaction domain , 2012, Proceedings of the National Academy of Sciences.

[10]  Steven J. M. Jones,et al.  Comprehensive molecular portraits of human breast tumours , 2013 .

[11]  Stefano Piccolo,et al.  Transduction of mechanical and cytoskeletal cues by YAP and TAZ , 2012, Nature Reviews Molecular Cell Biology.

[12]  Q. Ou,et al.  Yes-associated protein promotes tumour development in luminal epithelial derived breast cancer. , 2012, European journal of cancer.

[13]  U. Schmidt-Erfurth,et al.  Photodynamic therapy with verteporfin: A new treatment in ophthalmology , 2001, Seminars in ophthalmology.

[14]  E. Maltepe,et al.  Effect of Substrate Stiffness on Early Mouse Embryo Development , 2012, PloS one.

[15]  J. Coll,et al.  Inhibition of Apoptosis by Amphiregulin via an Insulin‐like Growth Factor‐1 Receptor—Dependent Pathway in Non‐Small Cell Lung Cancer Cell Lines , 2003, Annals of the New York Academy of Sciences.

[16]  Z. Nawaz,et al.  Loss of Yes-associated protein (YAP) expression is associated with estrogen and progesterone receptors negativity in invasive breast carcinomas , 2012, Breast Cancer Research and Treatment.

[17]  Cynthia A. Reinhart-King,et al.  Tensional homeostasis and the malignant phenotype. , 2005, Cancer cell.

[18]  Paul A. Janmey,et al.  Soft biological materials and their impact on cell function. , 2007, Soft matter.

[19]  Sanjay Kumar,et al.  Age-related dysfunction in mechanotransduction impairs differentiation of human mammary epithelial progenitors. , 2014, Cell reports.

[20]  Li Li,et al.  Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. , 2007, Genes & development.

[21]  Susan Goodin,et al.  Lapatinib: a dual inhibitor of human epidermal growth factor receptor tyrosine kinases. , 2008, Clinical Therapeutics.

[22]  B. Parvin,et al.  Molecular deconstruction, detection, and computational prediction of microenvironment-modulated cellular responses to cancer therapeutics. , 2014, Advanced drug delivery reviews.

[23]  Guanqing Ou,et al.  Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression , 2014, Nature Medicine.

[24]  Jianmin Zhang,et al.  YAP-dependent induction of amphiregulin identifies a non-cell-autonomous component of the Hippo pathway , 2009, Nature Cell Biology.

[25]  Jun O. Liu,et al.  Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. , 2012, Genes & development.

[26]  Dhara N. Amin,et al.  Resiliency and Vulnerability in the HER2-HER3 Tumorigenic Driver , 2010, Science Translational Medicine.

[27]  W. Jung,et al.  Yes-associated protein (YAP) is differentially expressed in tumor and stroma according to the molecular subtype of breast cancer. , 2014, International journal of clinical and experimental pathology.

[28]  Yang Yang,et al.  Osteoblasts Generate Harder, Stiffer, and More Delamination‐Resistant Mineralized Tissue on Titanium Than on Polystyrene, Associated With Distinct Tissue Micro‐ and Ultrastructure , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[29]  Sumin Zhao,et al.  An heregulin-EGFR-HER3 autocrine signaling axis can mediate acquired lapatinib resistance in HER2+ breast cancer models , 2013, Breast Cancer Research.

[30]  H. Ko,et al.  Glomerulocystic kidney disease in mice with a targeted inactivation of Wwtr1 , 2007, Proceedings of the National Academy of Sciences.

[31]  J. Christensen,et al.  MET Activation Mediates Resistance to Lapatinib Inhibition of HER2-Amplified Gastric Cancer Cells , 2012, Molecular Cancer Therapeutics.

[32]  S. Miyamoto,et al.  Amphiregulin regulates the activation of ERK and Akt through epidermal growth factor receptor and HER3 signals involved in the progression of pancreatic cancer , 2010, Cancer science.

[33]  D. Tripathy,et al.  Updates on the treatment of human epidermal growth factor receptor type 2-positive breast cancer , 2014, Current opinion in obstetrics & gynecology.

[34]  Brendon M. Baker,et al.  Deconstructing the third dimension – how 3D culture microenvironments alter cellular cues , 2012, Journal of Cell Science.

[35]  J. Rao,et al.  The role of Rho GTPase in cell stiffness and cisplatin resistance in ovarian cancer cells. , 2014, Integrative biology : quantitative biosciences from nano to macro.

[36]  Silviya Zustiak,et al.  Multiwell stiffness assay for the study of cell responsiveness to cytotoxic drugs , 2014, Biotechnology and bioengineering.

[37]  Suzanne F. Jones,et al.  Phase I safety, pharmacokinetics, and clinical activity study of lapatinib (GW572016), a reversible dual inhibitor of epidermal growth factor receptor tyrosine kinases, in heavily pretreated patients with metastatic carcinomas. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[38]  Genee Y. Lee,et al.  Three-dimensional culture models of normal and malignant breast epithelial cells , 2007, Nature Methods.

[39]  Carlos L Arteaga,et al.  Intrinsic and acquired resistance to HER2-targeted therapies in HER2 gene-amplified breast cancer: mechanisms and clinical implications. , 2012, Critical reviews in oncogenesis.

[40]  Adam J Engler,et al.  Preparation of Hydrogel Substrates with Tunable Mechanical Properties , 2010, Current protocols in cell biology.

[41]  Michael W Davidson,et al.  Force engages vinculin and promotes tumor progression by enhancing PI3K activation of phosphatidylinositol (3,4,5)-triphosphate. , 2014, Cancer research.

[42]  C. Murphy,et al.  The elastic modulus of Matrigel as determined by atomic force microscopy. , 2009, Journal of structural biology.

[43]  Sophie Lelièvre,et al.  beta4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. , 2002, Cancer cell.

[44]  M. Davidson,et al.  The cancer glycocalyx mechanically primes integrin-mediated growth and survival , 2014, Nature.

[45]  G. Ayers,et al.  Amphiregulin Exosomes Increase Cancer Cell Invasion , 2011, Current Biology.

[46]  T. Magnuson,et al.  Defects in Yolk Sac Vasculogenesis, Chorioallantoic Fusion, and Embryonic Axis Elongation in Mice with Targeted Disruption of Yap65 , 2006, Molecular and Cellular Biology.

[47]  A. Bardelli,et al.  TGFα and Amphiregulin Paracrine Network Promotes Resistance to EGFR Blockade in Colorectal Cancer Cells , 2014, Clinical Cancer Research.

[48]  Sirio Dupont.  Role of YAP/TAZ in mechanotransduction , 2011 .

[49]  William Pao,et al.  Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase , 2011, Proceedings of the National Academy of Sciences.