title: Galectin-3-induced cell spreading and motility relies on distinct signaling mechanisms compared to fibronectin.
abstract: Secreted galectin-3 often gets incorporated into extracellular matrix and is utilized by cancer cells for spreading, movement, and metastatic dissemination. Here we investigate molecular mechanisms by which galectin-3 brings about these effects and compare it with fibronectin. Imaging of cells spread on fibronectin showed stress fibers throughout cell body, however, galectin-3-induced formation of parallel actin bundles in the lamellipodial region resulting in unique morphological features. FRAP analysis showed that the actin turnover in the lamellipodial region was much higher in cells spread on galectin-3 as compared to that on fibronectin. Rac1 activation is correlated with lamellipodial organization on both the substrates. Activation of Akt and Rac1, the regulators of actin dynamics, show inverse correlation with each other on both galectin-3 and fibronectin. Activation of Erk however, remained similar. Further, inhibition of activation of Akt and Erk inhibited spreading and motility of cells on galectin-3 but not on fibronectin. The results very comprehensively demonstrate distinct signaling pathways that regulate microfilament organization, lamellipodial structures, spreading, and movement of cells plated on galectin-3 as opposed to fibronectin.
authors.affiliation: Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Sector 22, Kharghar, Navi Mumbai, 410210, India.
authors.forename: Shyam K
authors.initials: SK
authors.lastname: More
authors.affiliation: Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Sector 22, Kharghar, Navi Mumbai, 410210, India. schiplunkar@actrec.gov.in.
authors.forename: Shubhada V
authors.initials: SV
authors.lastname: Chiplunkar
authors.affiliation: Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Sector 22, Kharghar, Navi Mumbai, 410210, India.
authors.forename: Rajiv D
authors.initials: RD
authors.lastname: Kalraiya
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011554:Pseudopodia / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D005353:Fibronectins; D037502:Galectin 3; C485095:Lgals3 protein, mouse; D009479:Neuropeptides; C484602:Rac1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D020830:rac1 GTP-Binding Protein
keywords: Cell migration; Cell spreading; Fibronectin; Galectin-3; Lamellipodia; Microfilaments