We are interested in assessing whether mammalian cells have retained the signaling pathways and migration behavior that Dictyostelium use when they relay chemotactic signals during chemotaxis. Our work focuses on two aspects of neutrophil chemotaxis. First, we set out to determine the mechanism by which chemoattractants increase cAMP production. In Dictyostelium, ACA activation requires inputs from heterotrimeric G proteins, phosphoinositide-3 kinase (PI3K), and the target of rapamycin complex 2 (TORC2). A second project is aimed at understanding the role of signal relay during neutrophil chemotaxis. Chemokines have also been implicated in the progression of cancer, particularly during breast cancer metastasis. Moreover, a shift from mesenchymal (collective) to amoeboid movement is observed during metastasis. As cancer cells transition from clusters to single, amoeboid-like cells, they often migrate in a head-to-tail fashion and form files of cells that move along paths of least resistance. Metastatic cancer cells therefore revert to a very primitive and efficient mode of migration shared by hematopoietic and Dictyostelium cells. We hypothesize that the invasive potential of breast cancer cells is related to their ability to upregulate their chemotactic machinery, and is coupled to a dedifferentiation program that leads to primitive chemotactic behaviors such as amoeboid-like single cell migration and sheet/group migration.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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National Cancer Institute Division of Basic Sciences
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Saha, Piu; Yeoh, Beng San; Olvera, Rodrigo A et al. (2017) Bacterial Siderophores Hijack Neutrophil Functions. J Immunol 198:4293-4303
Liao, Xin-Hua; Meena, Netra Pal; Southall, Noel et al. (2016) A High-Throughput, Multi-Cell Phenotype Assay for the Identification of Novel Inhibitors of Chemotaxis/Migration. Sci Rep 6:22273
Majumdar, Ritankar; Tavakoli Tameh, Aidin; Parent, Carole A (2016) Exosomes Mediate LTB4 Release during Neutrophil Chemotaxis. PLoS Biol 14:e1002336
Lammers, Karen M; Chieppa, Marcello; Liu, Lunhua et al. (2015) Gliadin Induces Neutrophil Migration via Engagement of the Formyl Peptide Receptor, FPR1. PLoS One 10:e0138338
Moissoglu, Konstadinos; Majumdar, Ritankar; Parent, Carole A (2014) Cell migration: sinking in a gradient. Curr Biol 24:R23-5
Liu, Lunhua; Gritz, Derek; Parent, Carole A (2014) PKC?II acts downstream of chemoattractant receptors and mTORC2 to regulate cAMP production and myosin II activity in neutrophils. Mol Biol Cell 25:1446-57
Majumdar, Ritankar; Sixt, Michael; Parent, Carole A (2014) New paradigms in the establishment and maintenance of gradients during directed cell migration. Curr Opin Cell Biol 30:33-40
Afonso, Philippe V; McCann, Colin P; Kapnick, Senta M et al. (2013) Discoidin domain receptor 2 regulates neutrophil chemotaxis in 3D collagen matrices. Blood 121:1644-50
Parent, Carole A; Weiner, Orion D (2013) The symphony of cell movement: how cells orchestrate diverse signals and forces to control migration. Curr Opin Cell Biol 25:523-5
Afonso, Philippe V; Parent, Carole A (2013) [Leukotriene B(4): a lipid at the heart of inflammation]. Med Sci (Paris) 29:1083-5

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