Zena Werb
University of California, San Francisco
Matrix metalloproteinaseCancerInternal medicineEndocrinologyPathologyMolecular biologyStromal cellChemistryExtracellular matrixImmunologyMammary glandMetastasisAngiogenesisMorphogenesisCancer researchBreast cancerBiochemistryMedicineBiologyCell biology
Publications 525
#1Ori Maller (UCSF: University of California, San Francisco)H-Index: 9
#2Allison P. Drain (UCSF: University of California, San Francisco)H-Index: 5
Last. Valerie M. WeaverH-Index: 87
view all 26 authors...
Stromal stiffening accompanies malignancy, compromises treatment and promotes tumour aggression. Clarifying the molecular nature and the factors that regulate stromal stiffening in tumours should identify biomarkers to stratify patients for therapy and interventions to improve outcome. We profiled lysyl hydroxylase-mediated and lysyl oxidase-mediated collagen crosslinks and quantified the greatest abundance of total and complex collagen crosslinks in aggressive human breast cancer subtypes with ...
8 CitationsSource
Treatment resistance leads to cancer patient mortality. Therapeutic approaches that employ synthetic lethality to target mutational vulnerabilities in key tumor cell signaling pathways have proven effective in overcoming therapeutic resistance in some cancers. Yet, tumors are organs composed of malignant cells residing within a cellular and noncellular stroma. Tumor evolution and resistance to anticancer treatment are mediated through a dynamic and reciprocal dialogue with the tumor microenviron...
#1Kevin J. Metcalf (NU: Northwestern University)H-Index: 5
#2Blaise R. Kimmel (NU: Northwestern University)H-Index: 1
Last. Milan Mrksich (NU: Northwestern University)H-Index: 92
view all 10 authors...
This paper presents a method to synthetically tune atomically precise megamolecule nanobody-enzyme conjugates for prodrug cancer therapy. Previous efforts to create heterobifunctional protein conjugates suffered from heterogeneity in domain stoichiometry, which in part led to the failure of antibody-enzyme conjugates in clinical trials. We used the megamolecule approach to synthesize anti-HER2 nanobody-cytosine deaminase conjugates with tunable numbers of nanobody and enzyme domains in a single,...
#1Juliane Winkler (UCSF: University of California, San Francisco)H-Index: 7
#2Abisola Abisoye-Ogunniyan (UCSF: University of California, San Francisco)H-Index: 5
Last. Zena Werb (UCSF: University of California, San Francisco)H-Index: 180
view all 4 authors...
Tissues are dynamically shaped by bidirectional communication between resident cells and the extracellular matrix (ECM) through cell-matrix interactions and ECM remodelling. Tumours leverage ECM remodelling to create a microenvironment that promotes tumourigenesis and metastasis. In this review, we focus on how tumour and tumour-associated stromal cells deposit, biochemically and biophysically modify, and degrade tumour-associated ECM. These tumour-driven changes support tumour growth, increase ...
46 CitationsSource
#1A. Samocha (UCSF: University of California, San Francisco)H-Index: 1
Last. Jeroen P. Roose (University of California, Berkeley)
view all 15 authors...
Summary During puberty, robust morphogenesis occurs in the mammary gland; stem- and progenitor-cells develop into mature basal- and luminal-cells to form the ductal tree. The receptor signals that govern this process in mammary epithelial cells (MECs) are incompletely understood. The EGFR has been implicated and here we focused on EGFR’s downstream pathway component Rasgrp1. We find that Rasgrp1 dampens EGF-triggered signals in MECs. Biochemically and in vitro, Rasgrp1 perturbation results in in...
#2Juliane WinklerH-Index: 7
Last. Zena WerbH-Index: 180
view all 6 authors...
#1Juliane Winkler (UCSF: University of California, San Francisco)H-Index: 7
#2Weilun TanH-Index: 5
Last. Zena Werb (UCSF: University of California, San Francisco)H-Index: 180
view all 6 authors...
Metastasis is the major cause of cancer-related deaths due to insufficient therapeutic effects of conventional treatment. Individual tumor cells exhibit heterogeneous features and growth potentials within the same tumor. This intra-tumor heterogeneity influences the ability of the tumor to form metastasis. The underlying mechanisms of why some tumor cells can give rise to metastases, whereas others cannot are remarkably poorly understood. Tumor cells acquire complex properties in order to invade...
#1Catharina Hagerling (UCSF: University of California, San Francisco)H-Index: 8
#2Mark Owyong (UCSF: University of California, San Francisco)H-Index: 5
Last. Vicki Plaks (UCSF: University of California, San Francisco)H-Index: 22
view all 14 authors...
Novel biomarkers are required to discern between breast tumors that should be targeted for treatment from those that would never become clinically apparent and/or life threatening for patients. Moreover, therapeutics that specifically target breast cancer (BC) cells with tumor-initiating capacity to prevent recurrence are an unmet need. We investigated the clinical importance of LGR5 in BC and ductal carcinoma in situ (DCIS) to explore LGR5 as a biomarker and a therapeutic target. We stained BC ...
1 CitationsSource
#1Zena Werb (UCSF: University of California, San Francisco)H-Index: 180
#2Hugo Gonzalez (UCSF: University of California, San Francisco)H-Index: 4
Last. Eric Berens (UCSF: University of California, San Francisco)H-Index: 1
view all 4 authors...
Cancer cells within tumors exist in specialized niches in the microenvironment. The tumor cells are heterogeneous and can have properties as divergent as self-renewal, tumor initiation and repopulation potential, dormancy, evasion of cell death, and metastasis. Metastasis is the major cause of poor outcome in breast cancer. The microenvironment is critical for regulating multiple aspects of tumor progression and metastasis. Understanding the processes involved in metastasis is critical for devel...
#1Ryan T. Davis (UCI: University of California, Irvine)H-Index: 4
#2Kerrigan Blake (UCI: University of California, Irvine)H-Index: 2
Last. Devon A. Lawson (UCI: University of California, Irvine)H-Index: 22
view all 18 authors...
Although metastasis remains the cause of most cancer-related mortality, mechanisms governing seeding in distal tissues are poorly understood. Here, we establish a robust method for the identification of global transcriptomic changes in rare metastatic cells during seeding using single-cell RNA sequencing and patient-derived-xenograft models of breast cancer. We find that both primary tumours and micrometastases display transcriptional heterogeneity but micrometastases harbour a distinct transcri...
33 CitationsSource