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

Lin, Chun-Han; Pelissier, Fanny A.; Zhang, Hui; Lakins, Jon; Weaver, Valerie M.; Park, Catherine; LaBarge, Mark A.

doi:10.1091/mbc.E15-07-0456

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

Journal Article · Wed Sep 02 00:00:00 EDT 2015 · Molecular Biology of the Cell

DOI:https://doi.org/10.1091/mbc.E15-07-0456· OSTI ID:1378635

Lin, Chun-Han ^[1]; Pelissier, Fanny A. ^[2]; Zhang, Hui ^[3]; Lakins, Jon ^[4]; Weaver, Valerie M. ^[4]; Park, Catherine ^[3]; LaBarge, Mark A. ^[5]

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Univ. of California, Berkeley, CA (United States). Program in Comparative Biochemistry
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division; Bergen Univ. (Norway). Dept. of Biomedicine
Univ. of California, San Francisco, CA (United States).Dept. of Radiation Oncology
Univ. of California, San Francisco, CA (United States). Dept. of Surgery. Center for Bioengineering, Tissue Regeneration
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biological Systems and Engineering Division

Stiffness is a biophysical property of the extracellular matrix that modulates cellular functions, including proliferation, invasion, and differentiation, and it also may affect therapeutic responses. Therapeutic durability in cancer treatments remains a problem for both chemotherapies and pathway-targeted drugs, but the reasons for this are not well understood. Tumor progression is accompanied by changes in the biophysical properties of the tissue, and we asked whether matrix rigidity modulated the sensitive versus resistant states in HER2-amplified breast cancer cell responses to the HER2-targeted kinase inhibitor lapatinib. The antiproliferative effect of lapatinib was inversely proportional to the elastic modulus of the adhesive substrata. Down-regulation of the mechanosensitive transcription coactivators YAP and TAZ, either by siRNA or with the small-molecule YAP/TEAD inhibitor verteporfin, eliminated modulus-dependent lapatinib resistance. Reduction of YAP in vivo in mice also slowed the growth of implanted HER2-amplified tumors, showing a trend of increasing sensitivity to lapatinib as YAP decreased. Thus we address the role of stiffness in resistance to and efficacy of a HER2 pathway–targeted therapeutic via the mechanotransduction arm of the Hippo pathway.

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Research Organization:: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE; National Inst. of Health (NIH) (United States); Anita Tarr Turk Fund for Breast Cancer Research (United States)

Contributing Organization:: Univ. of California, Berkeley, CA (United States); Bergen Univ. (Norway)

Grant/Contract Number:: AC02-05CH11231; R00AG033176; R01AG040081; 20IB-0109

OSTI ID:: 1378635

Journal Information:: Molecular Biology of the Cell, Vol. 26, Issue 22; ISSN 1059-1524

Publisher:: American Society for Cell BiologyCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 93 works

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References (50)

Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts Calvo, Fernando; Ege, Nil; Grande-Garcia, Araceli Nature Cell Biology, Vol. 15, Issue 6 https://doi.org/10.1038/ncb2756	journal	May 2013
TGF and Amphiregulin Paracrine Network Promotes Resistance to EGFR Blockade in Colorectal Cancer Cells Hobor, S.; Van Emburgh, B. O.; Crowley, E. Clinical Cancer Research, Vol. 20, Issue 24 https://doi.org/10.1158/1078-0432.CCR-14-0774	journal	June 2014
Osteoblasts Generate Harder, Stiffer, and More Delamination-Resistant Mineralized Tissue on Titanium Than on Polystyrene, Associated With Distinct Tissue Micro- and Ultrastructure Saruwatari, Lei; Aita, Hideki; Butz, Frank Journal of Bone and Mineral Research, Vol. 20, Issue 11 https://doi.org/10.1359/JBMR.050703	journal	July 2005
Tensional homeostasis and the malignant phenotype Paszek, Matthew J.; Zahir, Nastaran; Johnson, Kandice R. Cancer Cell, Vol. 8, Issue 3 https://doi.org/10.1016/j.ccr.2005.08.010	journal	September 2005
The elastic modulus of Matrigel™ as determined by atomic force microscopy Soofi, Shauheen S.; Last, Julie A.; Liliensiek, Sara J. Journal of Structural Biology, Vol. 167, Issue 3 https://doi.org/10.1016/j.jsb.2009.05.005	journal	September 2009
HER2 signaling pathway activation and response of breast cancer cells to HER2-targeting agents is dependent strongly on the 3D microenvironment Weigelt, Britta; Lo, Alvin T.; Park, Catherine C. Breast Cancer Research and Treatment, Vol. 122, Issue 1 https://doi.org/10.1007/s10549-009-0502-2	journal	August 2009
Effect of Substrate Stiffness on Early Mouse Embryo Development Kolahi, Kevin S.; Donjacour, Annemarie; Liu, Xiaowei PLoS ONE, Vol. 7, Issue 7 https://doi.org/10.1371/journal.pone.0041717	journal	July 2012
Defects in Yolk Sac Vasculogenesis, Chorioallantoic Fusion, and Embryonic Axis Elongation in Mice with Targeted Disruption of Yap65 Morin-Kensicki, E. M.; Boone, B. N.; Howell, M. Molecular and Cellular Biology, Vol. 26, Issue 1 https://doi.org/10.1128/MCB.26.1.77-87.2006	journal	December 2005
Age-Related Dysfunction in Mechanotransduction Impairs Differentiation of Human Mammary Epithelial Progenitors Pelissier, Fanny A.; Garbe, James C.; Ananthanarayanan, Badriprasad Cell Reports, Vol. 7, Issue 6 https://doi.org/10.1016/j.celrep.2014.05.021	journal	June 2014
Multiwell stiffness assay for the study of cell responsiveness to cytotoxic drugs: Stiffness Assay for Toxicity Screening Zustiak, Silviya; Nossal, Ralph; Sackett, Dan L. Biotechnology and Bioengineering, Vol. 111, Issue 2 https://doi.org/10.1002/bit.25097	journal	September 2013
Three-dimensional culture models of normal and malignant breast epithelial cells Lee, Genee Y.; Kenny, Paraic A.; Lee, Eva H. Nature Methods, Vol. 4, Issue 4 https://doi.org/10.1038/nmeth1015	journal	March 2007
Sorafenib resistance and JNK signaling in carcinoma during extracellular matrix stiffening Nguyen, Thuy V.; Sleiman, Marianne; Moriarty, Timothy Biomaterials, Vol. 35, Issue 22 https://doi.org/10.1016/j.biomaterials.2014.03.058	journal	July 2014
Lapatinib: A dual inhibitor of human epidermal growth factor receptor tyrosine kinases Medina, P.; Goodin, S. Clinical Therapeutics, Vol. 30, Issue 8 https://doi.org/10.1016/j.clinthera.2008.08.008	journal	August 2008
Role of YAP/TAZ in mechanotransduction Dupont, Sirio; Morsut, Leonardo; Aragona, Mariaceleste Nature, Vol. 474, Issue 7350 https://doi.org/10.1038/nature10137	journal	June 2011
Soft biological materials and their impact on cell function Levental, Ilya; Georges, Penelope C.; Janmey, Paul A. Soft Matter, Vol. 3, Issue 3 https://doi.org/10.1039/B610522J	journal	January 2007
Intrinsic and Acquired Resistance to HER2-Targeted Therapies in HER2 Gene-Amplified Breast Cancer: Mechanisms and Clinical Implications Rexer, Brent N.; Arteaga, Carlos L. Critical Reviews™ in Oncogenesis, Vol. 17, Issue 1 https://doi.org/10.1615/CritRevOncog.v17.i1.20	journal	January 2012
Yes-associated protein (YAP) functions as a tumor suppressor in breast Yuan, M.; Tomlinson, V.; Lara, R. Cell Death & Differentiation, Vol. 15, Issue 11 https://doi.org/10.1038/cdd.2008.108	journal	July 2008
Updates on the treatment of human epidermal growth factor receptor type 2-positive breast cancer Kim, Miriam; Agarwal, Surbhi; Tripathy, Debu Current Opinion in Obstetrics and Gynecology, Vol. 26, Issue 1 https://doi.org/10.1097/GCO.0000000000000043	journal	January 2014
Deconstructing the third dimension – how 3D culture microenvironments alter cellular cues Baker, Brendon M.; Chen, Christopher S. Journal of Cell Science, Vol. 125, Issue 13 https://doi.org/10.1242/jcs.079509	journal	July 2012
Amphiregulin regulates the activation of ERK and Akt through epidermal growth factor receptor and HER3 signals involved in the progression of pancreatic cancer Yotsumoto, Fusanori; Fukami, Tatsuya; Yagi, Hiroshi Cancer Science, Vol. 101, Issue 11 https://doi.org/10.1111/j.1349-7006.2010.01671.x	journal	July 2010
β4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium Weaver, Valerie M.; Lelièvre, Sophie; Lakins, Johnathon N. Cancer Cell, Vol. 2, Issue 3 https://doi.org/10.1016/S1535-6108(02)00125-3	journal	September 2002
Force Engages Vinculin and Promotes Tumor Progression by Enhancing PI3K Activation of Phosphatidylinositol (3,4,5)-Triphosphate Rubashkin, Matthew G.; Cassereau, Luke; Bainer, Russell Cancer Research, Vol. 74, Issue 17 https://doi.org/10.1158/0008-5472.CAN-13-3698	journal	September 2014
Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP Liu-Chittenden, Y.; Huang, B.; Shim, J. S. Genes & Development, Vol. 26, Issue 12 https://doi.org/10.1101/gad.192856.112	journal	June 2012
Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression Mouw, Janna K.; Yui, Yoshihiro; Damiano, Laura Nature Medicine, Vol. 20, Issue 4 https://doi.org/10.1038/nm.3497	journal	March 2014
Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase Garrett, J. T.; Olivares, M. G.; Rinehart, C. Proceedings of the National Academy of Sciences, Vol. 108, Issue 12 https://doi.org/10.1073/pnas.1016140108	journal	March 2011
Classifying the estrogen receptor status of breast cancers by expression profiles reveals a poor prognosis subpopulation exhibiting high expression of the ERBB2 receptor Kun, Yu; How, Lee Chee; Hoon, Tan Puay Human Molecular Genetics, Vol. 12, Issue 24 https://doi.org/10.1093/hmg/ddg347	journal	December 2003
Photodynamic therapy with verteporfin: A new treatment in ophthalmology Michels, Stephan; Schmidt-Erfurth, Ursula Seminars in Ophthalmology, Vol. 16, Issue 4 https://doi.org/10.1076/soph.16.4.201.10298	journal	January 2001
A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes Neve, Richard M.; Chin, Koei; Fridlyand, Jane Cancer Cell, Vol. 10, Issue 6 https://doi.org/10.1016/j.ccr.2006.10.008	journal	December 2006
Loss of Yes-associated protein (YAP) expression is associated with estrogen and progesterone receptors negativity in invasive breast carcinomas Tufail, Rozina; Jorda, Mercy; Zhao, Wei Breast Cancer Research and Treatment, Vol. 131, Issue 3 https://doi.org/10.1007/s10549-011-1435-0	journal	March 2011
MET Activation Mediates Resistance to Lapatinib Inhibition of HER2-Amplified Gastric Cancer Cells Chen, C. -T.; Kim, H.; Liska, D. Molecular Cancer Therapeutics, Vol. 11, Issue 3 https://doi.org/10.1158/1535-7163.MCT-11-0754	journal	January 2012
Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control Zhao, B.; Wei, X.; Li, W. Genes & Development, Vol. 21, Issue 21 https://doi.org/10.1101/gad.1602907	journal	November 2007
Inhibition of Apoptosis by Amphiregulin via an Insulin-like Growth Factor-1 Receptor-dependent Pathway in Non-small Cell Lung Cancer Cell Lines Hurbin, Amandine; Dubrez, Laurence; Coll, Jean-Luc Journal of Biological Chemistry, Vol. 277, Issue 51 https://doi.org/10.1074/jbc.M207584200	journal	September 2002
Glomerulocystic kidney disease in mice with a targeted inactivation of Wwtr1 Hossain, Z.; Ali, S. M.; Ko, H. L. Proceedings of the National Academy of Sciences, Vol. 104, Issue 5 https://doi.org/10.1073/pnas.0605266104	journal	January 2007
Novel Mechanism of Lapatinib Resistance in HER2-Positive Breast Tumor Cells: Activation of AXL Liu, L.; Greger, J.; Shi, H. Cancer Research, Vol. 69, Issue 17 https://doi.org/10.1158/0008-5472.CAN-08-4490	journal	August 2009
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 Burris, Howard A.; Hurwitz, Herbert I.; Dees, E. Claire Journal of Clinical Oncology, Vol. 23, Issue 23 https://doi.org/10.1200/JCO.2005.16.584	journal	August 2005
Matrix stiffness modulates proliferation, chemotherapeutic response, and dormancy in hepatocellular carcinoma cells Schrader, Jörg; Gordon-Walker, Timothy T.; Aucott, Rebecca L. Hepatology, Vol. 53, Issue 4 https://doi.org/10.1002/hep.24108	journal	April 2011
Yes-associated protein promotes tumour development in luminal epithelial derived breast cancer Wang, Xiaodan; Su, Lili; Ou, Qishui European Journal of Cancer, Vol. 48, Issue 8 https://doi.org/10.1016/j.ejca.2011.10.001	journal	May 2012
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 Rusnak, D. W.; Alligood, K. J.; Mullin, R. J. Cell Proliferation, Vol. 40, Issue 4 https://doi.org/10.1111/j.1365-2184.2007.00455.x	journal	August 2007
The cancer glycocalyx mechanically primes integrin-mediated growth and survival Paszek, Matthew J.; DuFort, Christopher C.; Rossier, Olivier Nature, Vol. 511, Issue 7509 https://doi.org/10.1038/nature13535	journal	June 2014
YAP-dependent induction of amphiregulin identifies a non-cell-autonomous component of the Hippo pathway Zhang, Jianmin; Ji, Jun-Yuan; Yu, Min Nature Cell Biology, Vol. 11, Issue 12 https://doi.org/10.1038/ncb1993	journal	November 2009
Molecular deconstruction, detection, and computational prediction of microenvironment-modulated cellular responses to cancer therapeutics LaBarge, Mark A.; Parvin, Bahram; Lorens, James B. Advanced Drug Delivery Reviews, Vol. 69-70 https://doi.org/10.1016/j.addr.2014.02.009	journal	April 2014
An heregulin-EGFR-HER3 autocrine signaling axis can mediate acquired lapatinib resistance in HER2+ breast cancer models Xia, Wenle; Petricoin, Emanual F.; Zhao, Sumin Breast Cancer Research, Vol. 15, Issue 5 https://doi.org/10.1186/bcr3480	journal	September 2013
The Hippo pathway target, YAP, promotes metastasis through its TEAD-interaction domain Lamar, J. M.; Stern, P.; Liu, H. Proceedings of the National Academy of Sciences, Vol. 109, Issue 37 https://doi.org/10.1073/pnas.1212021109	journal	August 2012
Amphiregulin Exosomes Increase Cancer Cell Invasion Higginbotham, James N.; Demory Beckler, Michelle; Gephart, Jonathan D. Current Biology, Vol. 21, Issue 9 https://doi.org/10.1016/j.cub.2011.03.043	journal	May 2011
The role of Rho GTPase in cell stiffness and cisplatin resistance in ovarian cancer cells Sharma, Shivani; Santiskulvong, Chintda; Rao, Jianyu Integr. Biol., Vol. 6, Issue 6 https://doi.org/10.1039/C3IB40246K	journal	January 2014
SNHG7 is a lncRNA oncogene controlled by Insulin-like Growth Factor signaling through a negative feedback loop to tightly regulate proliferation Boone, David N.; Warburton, Andrew; Som, Sreeroopa Scientific Reports, Vol. 10, Issue 1 https://doi.org/10.1038/s41598-020-65109-7	journal	May 2020
Comprehensive molecular portraits of human breast tumours Charles, Perou, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/hyeb-c392	text	January 2012
Defects in Yolk Sac Vasculogenesis, Chorioallantoic Fusion, and Embryonic Axis Elongation in Mice with Targeted Disruption of Yap65 M., Howell,; R., Stonebraker, J.; J., Teed, The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/3nn5-1a33	text	January 2006
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 Paul, Marcom,; Andrew, Stead,; Claire, Dees, E. The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/3qnq-jc02	text	January 2005
Inhibition of Apoptosis by Amphiregulin via an Insulin-like Growth Factor-1 Receptor-Dependent Pathway in Non-Small Cell Lung Cancer Cell Lines Hurbin, Amandine; Dubrez, Laurence; Coll, Jean-Luc Annals of the New York Academy of Sciences, Vol. 1010, Issue 1 https://doi.org/10.1196/annals.1299.065	journal	December 2003

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