Michelle C Mendoza

Michelle C Mendoza
University of Utah | UOU · Department of Oncological Sciences

PhD

About

26
Publications
2,132
Reads
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2,005
Citations
Citations since 2016
11 Research Items
1471 Citations
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
2016201720182019202020212022050100150200
Introduction
Skills and Expertise
Additional affiliations
January 2014 - August 2015
University of California, San Francisco
Position
  • Professor (Assistant)
September 2011 - December 2013
Harvard Medical School
Position
  • PostDoc Position
January 2006 - December 2013
Harvard Medical School
Position
  • PostDoc Position

Publications

Publications (26)
Article
Full-text available
Early lung cancer lesions develop within a unique microenvironment that undergoes constant cyclic stretch from respiration. While tumor stiffening is an established driver of tumor progression, the contribution of stress and strain to lung cancer is unknown. We developed tissue scale finite element models of lung tissue to test how early lesions al...
Article
Full-text available
The RAS→RAF→MEK→ERK pathway is hyperactivated in the majority of human lung adenocarcinoma (LUAD). However, the initial activating mutations induce homeostatic feedback mechanisms that limit ERK activity. How ERK activation reaches the tumor-promoting levels that overcome the feedback and drive malignant progression is unclear. We show here that th...
Preprint
Full-text available
Cell migration is essential to physiological and pathological biology. Migration is driven by the motion of a leading edge, in which actin polymerization pushes against the edge and adhesions transmit traction to the substrate while membrane tension increases. How the actin and adhesions synergistically control edge protrusion remains elusive. We a...
Article
Full-text available
Cancer cells undergo lineage switching during natural progression and in response to therapy. NKX2-1 loss in human and murine lung adenocarcinoma leads to invasive mucinous adenocarcinoma (IMA), a lung cancer subtype that exhibits gastric differentiation and harbors a distinct spectrum of driver oncogenes. In murine BRAFV600E driven lung adenocarci...
Preprint
Full-text available
Lung cancer remains a leading cause of cancer death, with unclear mechanisms driving the transition to aggressive cancer with poor prognosis. The RAS→RAF→MEK→ERK pathway is hyper-activated in ~50% of human lung adenocarcinoma (LUAD). An initial activating mutation induces homeostatic feedback mechanisms that limit ERK activity. Additional, undefine...
Conference Paper
Hyperactivation of the PI3K/AKT signaling pathway occurs in most metastatic melanomas and increased PI3K/AKT pathway activity correlates with disease progression. The serine/threonine kinase, AKT, represents a major signaling hub within the pathway and consists of three highly conserved paralogs that have both distinct and overlapping functions. Ac...
Preprint
Full-text available
Cancer cells often undergo lineage switching during their natural progression and in response to therapy. Lung adenocarcinomas (LUADs) exhibit a variety of differentiation states accompanied by dysregulation of lineage-specific transcription factors such as NKX2-1. Loss of NKX2-1 in human and murine LUAD leads to invasive mucinous adenocarcinoma (I...
Article
Alterations in the PI3K/AKT pathway occur in up to 70% of melanomas and are associated with disease progression. The three AKT paralogs are highly conserved but data suggest they have distinct functions. Activating mutations of AKT1 and AKT3 occur in human melanoma but their role in melanoma formation and metastasis remains unclear. Using an establ...
Article
Full-text available
Cell migration is essential to embryonic development, wound healing, and cancer cell dissemination. Cells move via leading-edge protrusion, substrate adhesion, and retraction of the cell's rear. The molecular mechanisms by which extracellular cues signal to the actomyosin cytoskeleton to control these motility mechanics are poorly understood. The g...
Article
Full-text available
Cells move through perpetual protrusion and retraction cycles at the leading edge. These cycles are coordinated with substrate adhesion and retraction of the cell rear. We tracked spatial and temporal fluctuations in the molecular activities of individual moving cells to elucidate how extracellular signal-regulated kinase (ERK) signaling controlled...
Article
Full-text available
Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase (RTK) that controls cell proliferation, growth, survival, metabolism, and migration by activating the PI3K (phosphatidylinositol 3-kinase)-AKT and ERK (extracellular signal-regulated kinase)-RSK (ribosomal S6 kinase) pathways. EGFR signaling to these pathways is temporally and sp...
Article
The WAVE2 Regulatory Complex (WRC) induces actin polymerization by activating the actin nucleator Arp2/3. Polymerizing actin pushes against the cell membrane and induces dramatic edge protrusions. In order to properly control such changes in cell morphology and function, cells have evolved multiple methods to tightly regulate WRC and Arp2/3 activit...
Article
Quantitative fluorescent speckle microscopy (QFSM) is a live-cell imaging method to analyze the dynamics of macromolecular assemblies with high spatial and temporal resolution. Its greatest successes were in the analysis of actin filament and adhesion dynamics in the context of cell migration and microtubule dynamics in interphase and the meiotic/m...
Article
Full-text available
The acquisition of an invasive phenotype is a critical turning point for malignant tumor cells. CMTM8, a potential tumor suppressor, is frequently down-regulated in solid tumors, and its overexpression induces tumor cell apoptosis. Here, we identify a new role for CMTM8 in regulating tumor cell migration. Reducing CMTM8 expression in HepG2 hepatoce...
Article
The Ras-extracellular signal-regulated kinase (Ras-ERK) and phosphatidylinositol 3-kinase-mammalian target of rapamycin (PI3K-mTOR) signaling pathways are the chief mechanisms for controlling cell survival, differentiation, proliferation, metabolism, and motility in response to extracellular cues. Components of these pathways were among the first t...
Article
Cell movement begins with a leading edge protrusion, which is stabilized by nascent adhesions and retracted by mature adhesions. The ERK-MAPK (extracellular signal-regulated kinase-mitogen-activated protein kinase) localizes to protrusions and adhesions, but how it regulates motility is not understood. We demonstrate that ERK controls protrusion in...
Article
ERK-MAPK is activated by dual phosphorylation of its activation loop TEY motif by the MEK-MAPKK. ERK cytoplasmic activity should be measured by assaying both the level of dually phosphorylated ERK and the level of phosphorylated substrate. We describe two complementary methods for quantitatively measuring ERK activity toward the cytoplasmic p90 rib...
Article
Full-text available
Chaperonin containing TCP-1 (CCT) is a large multisubunit complex that mediates protein folding in eukaryotic cells. CCT participates in the folding of newly synthesized polypeptides, including actin, tubulin, and several cell cycle regulators; therefore, CCT plays an important role in cytoskeletal organization and cell division. Here we identify t...
Article
Full-text available
The MEK and extracellular signal-regulated kinase/mitogen-activated protein kinase proteins are established regulators of multicellular development and cell movement. By combining traditional genetic and biochemical assays with a statistical analysis of global gene expression profiles, we discerned a genetic interaction between Dictyostelium discoi...
Article
Three Akt isoforms differentially control cell survival, growth, proliferation, metabolism, and motility. In this issue of Molecular Cell, Brognard et al. (2007) report that two PHLPP phosphatases specifically downregulate the Akts to control the activity of isoform-specific substrates.
Article
Both prokaryote and eukaryote cells can sense and move up chemical concentration gradients (chemotax). As a means of finding food sources during vegetative growth, Dictyostelium discoideum naturally chemotaxes toward chemicals released by bacteria. As part of its developmental life cycle, D. discoideum chemotaxes towards cAMP. This chapter describe...
Article
Full-text available
MEK/extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase signaling is imperative for proper chemotaxis. Dictyostelium mek1− (MEK1 null) and erk1− cells exhibit severe defects in cell polarization and directional movement, but the molecules responsible for the mek1− and erk1− chemotaxis defects are unknown. Here, we describe...
Article
Thesis (Ph. D.)--University of California, San Diego, 2005. Vita. Includes bibliographical references (leaves 105-117).

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