Alissa Weaver
Faculty Member
Last active: 4/2/2019

Profile

Cell motility is important for a number of physiologic and pathologic processes, including wound healing, immune system function, axon guidance, and cancer cell metastasis. In order for a cell to move, it must rapidly rearrange its actin cytoskeleton to produce the required cell shape changes and to generate force. Among the various forms of actin structures in cells, the most dynamic (assembled and disassembled in a matter of seconds) are the branched actin filament networks nucleated by the Arp2/3 protein complex. Arp2/3 complex is essential for plasma membrane protrusion at the leading edge of migrating cells and is also important in such processes as endocytosis, cell-cell junction formation, and the formation of subcellular structures used for cancer cell invasion (invadopodia).
Activation of Arp2/3 complex in cells occurs in response to a variety of signals, including from growth factors, src family kinases, and rho GTPases. Cellular activators include members of the Wiskott-Aldrich Syndrome family of proteins (WASps) and cortactin, a src kinase substrate that is overexpressed in a number of epithelial cancers. A major goal of the laboratory is to understand how Arp2/3-activators and associated signaling molecules contribute to cell motility and cancer invasion. We use a variety of techniques including siRNA, live-cell imaging, and biochemistry. Specific projects include: 1) cortactin and WASp family function in lamellipodial protrusion and cell motility; 2) actin assembly in membrane trafficking and autocrine secretion; 3) role of cortactin in head and neck squamous carcinoma progression; 4) molecular regulation of invadopodia; 5) determining critical parameters for invasion of breast cancer cells in three dimensions; and 6) interdisciplinary projects focused on mathematical modeling of cancer invasion.



Figure 1: Breast cancer cell stained with rhodamine-phalloidin to reveal filamentous actin (left panel) at sites of invasion into fluorescent basement membrane (middle panel: FITC-fibronectin). Right panel: merge of images.
. . . . . . . . . .

Publications

The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. Théry C, Witwer KW, Aikawa E, Alcaraz MJ, Anderson JD, Andriantsitohaina R, Antoniou A, Arab T, Archer F, Atkin-Smith GK, Ayre DC, Bach JM, Bachurski D, Baharvand H, Balaj L, Baldacchino S, Bauer NN, Baxter AA, Bebawy M, Beckham C, Bedina Zavec A, Benmoussa A, Berardi AC, Bergese P, Bielska E, Blenkiron C, Bobis-Wozowicz S, Boilard E, Boireau W, Bongiovanni A, Borràs FE, Bosch S, Boulanger CM, Breakefield X, Breglio AM, Brennan MÁ, Brigstock DR, Brisson A, Broekman ML, Bromberg JF, Bryl-Górecka P, Buch S, Buck AH, Burger D, Busatto S, Buschmann D, Bussolati B, Buzás EI, Byrd JB, Camussi G, Carter DR, Caruso S, Chamley LW, Chang YT, Chen C, Chen S, Cheng L, Chin AR, Clayton A, Clerici SP, Cocks A, Cocucci E, Coffey RJ, Cordeiro-da-Silva A, Couch Y, Coumans FA, Coyle B, Crescitelli R, Criado MF, D'Souza-Schorey C, Das S, Datta Chaudhuri A, de Candia P, De Santana EF, De Wever O, Del Portillo HA, Demaret T, Deville S, Devitt A, Dhondt B, Di Vizio D, Dieterich LC, Dolo V, Dominguez Rubio AP, Dominici M, Dourado MR, Driedonks TA, Duarte FV, Duncan HM, Eichenberger RM, Ekström K, El Andaloussi S, Elie-Caille C, Erdbrügger U, Falcón-Pérez JM, Fatima F, Fish JE, Flores-Bellver M, Försönits A, Frelet-Barrand A, Fricke F, Fuhrmann G, Gabrielsson S, Gámez-Valero A, Gardiner C, Gärtner K, Gaudin R, Gho YS, Giebel B, Gilbert C, Gimona M, Giusti I, Goberdhan DC, Görgens A, Gorski SM, Greening DW, Gross JC, Gualerzi A, Gupta GN, Gustafson D, Handberg A, Haraszti RA, Harrison P, Hegyesi H, Hendrix A, Hill AF, Hochberg FH, Hoffmann KF, Holder B, Holthofer H, Hosseinkhani B, Hu G, Huang Y, Huber V, Hunt S, Ibrahim AG, Ikezu T, Inal JM, Isin M, Ivanova A, Jackson HK, Jacobsen S, Jay SM, Jayachandran M, Jenster G, Jiang L, Johnson SM, Jones JC, Jong A, Jovanovic-Talisman T, Jung S, Kalluri R, Kano SI, Kaur S, Kawamura Y, Keller ET, Khamari D, Khomyakova E, Khvorova A, Kierulf P, Kim KP, Kislinger T, Klingeborn M, Klinke DJ, Kornek M, Kosanović MM, Kovács ÁF, Krämer-Albers EM, Krasemann S, Krause M, Kurochkin IV, Kusuma GD, Kuypers S, Laitinen S, Langevin SM, Languino LR, Lannigan J, Lässer C, Laurent LC, Lavieu G, Lázaro-Ibáñez E, Le Lay S, Lee MS, Lee YXF, Lemos DS, Lenassi M, Leszczynska A, Li IT, Liao K, Libregts SF, Ligeti E, Lim R, Lim SK, Linē A, Linnemannstöns K, Llorente A, Lombard CA, Lorenowicz MJ, Lörincz ÁM, Lötvall J, Lovett J, Lowry MC, Loyer X, Lu Q, Lukomska B, Lunavat TR, Maas SL, Malhi H, Marcilla A, Mariani J, Mariscal J, Martens-Uzunova ES, Martin-Jaular L, Martinez MC, Martins VR, Mathieu M, Mathivanan S, Maugeri M, McGinnis LK, McVey MJ, Meckes DG, Meehan KL, Mertens I, Minciacchi VR, Möller A, Møller Jørgensen M, Morales-Kastresana A, Morhayim J, Mullier F, Muraca M, Musante L, Mussack V, Muth DC, Myburgh KH, Najrana T, Nawaz M, Nazarenko I, Nejsum P, Neri C, Neri T, Nieuwland R, Nimrichter L, Nolan JP, Nolte-'t Hoen EN, Noren Hooten N, O'Driscoll L, O'Grady T, O'Loghlen A, Ochiya T, Olivier M, Ortiz A, Ortiz LA, Osteikoetxea X, Østergaard O, Ostrowski M, Park J, Pegtel DM, Peinado H, Perut F, Pfaffl MW, Phinney DG, Pieters BC, Pink RC, Pisetsky DS, Pogge von Strandmann E, Polakovicova I, Poon IK, Powell BH, Prada I, Pulliam L, Quesenberry P, Radeghieri A, Raffai RL, Raimondo S, Rak J, Ramirez MI, Raposo G, Rayyan MS, Regev-Rudzki N, Ricklefs FL, Robbins PD, Roberts DD, Rodrigues SC, Rohde E, Rome S, Rouschop KM, Rughetti A, Russell AE, Saá P, Sahoo S, Salas-Huenuleo E, Sánchez C, Saugstad JA, Saul MJ, Schiffelers RM, Schneider R, Schøyen TH, Scott A, Shahaj E, Sharma S, Shatnyeva O, Shekari F, Shelke GV, Shetty AK, Shiba K, Siljander PR, Silva AM, Skowronek A, Snyder OL, Soares RP, Sódar BW, Soekmadji C, Sotillo J, Stahl PD, Stoorvogel W, Stott SL, Strasser EF, Swift S, Tahara H, Tewari M, Timms K, Tiwari S, Tixeira R, Tkach M, Toh WS, Tomasini R, Torrecilhas AC, Tosar JP, Toxavidis V, Urbanelli L, Vader P, van Balkom BW, van der Grein SG, Van Deun J, van Herwijnen MJ, Van Keuren-Jensen K, van Niel G, van Royen ME, van Wijnen AJ, Vasconcelos MH, Vechetti IJ, Veit TD, Vella LJ, Velot É, Verweij FJ, Vestad B, Viñas JL, Visnovitz T, Vukman KV, Wahlgren J, Watson DC, Wauben MH, Weaver A, Webber JP, Weber V, Wehman AM, Weiss DJ, Welsh JA, Wendt S, Wheelock AM, Wiener Z, Witte L, Wolfram J, Xagorari A, Xander P, Xu J, Yan X, Yáñez-Mó M, Yin H, Yuana Y, Zappulli V, Zarubova J, Žėkas V, Zhang JY, Zhao Z, Zheng L, Zheutlin AR, Zickler AM, Zimmermann P, Zivkovic AM, Zocco D, Zuba-Surma EK (2018) J Extracell Vesicles 7(1): 1535750
    › Primary publication · 30637094 (PubMed) · PMC6322352 (PubMed Central)
  2. Quantitative Proteomic Analysis of Small and Large Extracellular Vesicles (EVs) Reveals Enrichment of Adhesion Proteins in Small EVs. Jimenez L, Yu H, McKenzie AJ, Franklin JL, Patton JG, Liu Q, Weaver AM (2019) J Proteome Res 18(3): 947-959
    › Primary publication · 30608700 (PubMed) · PMC6411421 (PubMed Central)
  3. Exosome secretion promotes chemotaxis of cancer cells. Sung BH, Weaver AM (2017) Cell Adh Migr 11(2): 187-195
    › Primary publication · 28129015 (PubMed) · PMC5351719 (PubMed Central)
  4. Extracellular Vesicles: Unique Intercellular Delivery Vehicles. Maas SLN, Breakefield XO, Weaver AM (2017) Trends Cell Biol 27(3): 172-188
    › Primary publication · 27979573 (PubMed) · PMC5318253 (PubMed Central)
  5. Circular RNAs are down-regulated in KRAS mutant colon cancer cells and can be transferred to exosomes. Dou Y, Cha DJ, Franklin JL, Higginbotham JN, Jeppesen DK, Weaver AM, Prasad N, Levy S, Coffey RJ, Patton JG, Zhang B (2016) Sci Rep : 37982
    › Primary publication · 27892494 (PubMed) · PMC5125100 (PubMed Central)
  6. Cortactin promotes exosome secretion by controlling branched actin dynamics. Sinha S, Hoshino D, Hong NH, Kirkbride KC, Grega-Larson NE, Seiki M, Tyska MJ, Weaver AM (2016) J Cell Biol 214(2): 197-213
    › Primary publication · 27402952 (PubMed) · PMC4949450 (PubMed Central)
  7. Laminin-111 peptide C16 regulates invadopodia activity of malignant cells through β1 integrin, Src and ERK 1/2. Siqueira AS, Pinto MP, Cruz MC, Smuczek B, Cruz KS, Barbuto JA, Hoshino D, Weaver AM, Freitas VM, Jaeger RG (2016) Oncotarget 7(30): 47904-47917
    › Primary publication · 27323814 (PubMed) · PMC5216987 (PubMed Central)
  8. KRAS-MEK Signaling Controls Ago2 Sorting into Exosomes. McKenzie AJ, Hoshino D, Hong NH, Cha DJ, Franklin JL, Coffey RJ, Patton JG, Weaver AM (2016) Cell Rep 15(5): 978-987
    › Primary publication · 27117408 (PubMed) · PMC4857875 (PubMed Central)
  9. Regulation of invadopodia by mechanical signaling. Parekh A, Weaver AM (2016) Exp Cell Res 343(1): 89-95
    › Primary publication · 26546985 (PubMed) · PMC4851576 (PubMed Central)
  10. PI(3,5)P2 controls endosomal branched actin dynamics by regulating cortactin-actin interactions. Hong NH, Qi A, Weaver AM (2015) J Cell Biol 210(5): 753-69
    › Primary publication · 26323691 (PubMed) · PMC4555817 (PubMed Central)
  11. Biogenesis, delivery, and function of extracellular RNA. Patton JG, Franklin JL, Weaver AM, Vickers K, Zhang B, Coffey RJ, Ansel KM, Blelloch R, Goga A, Huang B, L'Etoille N, Raffai RL, Lai CP, Krichevsky AM, Mateescu B, Greiner VJ, Hunter C, Voinnet O, McManus MT (2015) J Extracell Vesicles : 27494
    › Primary publication · 26320939 (PubMed) · PMC4553266 (PubMed Central)
  12. KRAS-dependent sorting of miRNA to exosomes. Cha DJ, Franklin JL, Dou Y, Liu Q, Higginbotham JN, Demory Beckler M, Weaver AM, Vickers K, Prasad N, Levy S, Zhang B, Coffey RJ, Patton JG (2015) Elife : e07197
    › Primary publication · 26132860 (PubMed) · PMC4510696 (PubMed Central)
  13. Proteolysis of EphA2 Converts It from a Tumor Suppressor to an Oncoprotein. Koshikawa N, Hoshino D, Taniguchi H, Minegishi T, Tomari T, Nam SO, Aoki M, Sueta T, Nakagawa T, Miyamoto S, Nabeshima K, Weaver AM, Seiki M (2015) Cancer Res 75(16): 3327-39
    › Primary publication · 26130649 (PubMed) · PMC4682662 (PubMed Central)
  14. Linking patient outcome to high throughput protein expression data identifies novel regulators of colorectal adenocarcinoma aggressiveness. French CL, Ye F, Revetta F, Zhang B, Coffey RJ, Washington MK, Deane NG, Beauchamp RD, Weaver AM (2015) F1000Res : 99
    › Primary publication · 26097693 (PubMed) · PMC4457132 (PubMed Central)
  15. Directional cell movement through tissues is controlled by exosome secretion. Sung BH, Ketova T, Hoshino D, Zijlstra A, Weaver AM (2015) Nat Commun : 7164
    › Primary publication · 25968605 (PubMed) · PMC4435734 (PubMed Central)
  16. Activating PIK3CA Mutations Induce an Epidermal Growth Factor Receptor (EGFR)/Extracellular Signal-regulated Kinase (ERK) Paracrine Signaling Axis in Basal-like Breast Cancer. Young CD, Zimmerman LJ, Hoshino D, Formisano L, Hanker AB, Gatza ML, Morrison MM, Moore PD, Whitwell CA, Dave B, Stricker T, Bhola NE, Silva GO, Patel P, Brantley-Sieders DM, Levin M, Horiates M, Palma NA, Wang K, Stephens PJ, Perou CM, Weaver AM, O'Shaughnessy JA, Chang JC, Park BH, Liebler DC, Cook RS, Arteaga CL (2015) Mol Cell Proteomics 14(7): 1959-76
    › Primary publication · 25953087 (PubMed) · PMC4587316 (PubMed Central)
  17. Response of head and neck squamous cell carcinoma cells carrying PIK3CA mutations to selected targeted therapies. Wirtz ED, Hoshino D, Maldonado AT, Tyson DR, Weaver AM (2015) JAMA Otolaryngol Head Neck Surg 141(6): 543-9
    › Primary publication · 25855885 (PubMed) · PMC4474763 (PubMed Central)
  18. Arrestins regulate cell spreading and motility via focal adhesion dynamics. Cleghorn WM, Branch KM, Kook S, Arnette C, Bulus N, Zent R, Kaverina I, Gurevich EV, Weaver AM, Gurevich VV (2015) Mol Biol Cell 26(4): 622-35
    › Primary publication · 25540425 (PubMed) · PMC4325834 (PubMed Central)
  19. 3D collagen alignment limits protrusions to enhance breast cancer cell persistence. Riching KM, Cox BL, Salick MR, Pehlke C, Riching AS, Ponik SM, Bass BR, Crone WC, Jiang Y, Weaver AM, Eliceiri KW, Keely PJ (2014) Biophys J 107(11): 2546-58
    › Primary publication · 25468334 (PubMed) · PMC4255204 (PubMed Central)
  20. A three-dimensional computational model of collagen network mechanics. Lee B, Zhou X, Riching K, Eliceiri KW, Keely PJ, Guelcher SA, Weaver AM, Jiang Y (2014) PLoS One 9(11): e111896
    › Primary publication · 25386649 (PubMed) · PMC4227658 (PubMed Central)
  21. Role of adenosine A2B receptor signaling in contribution of cardiac mesenchymal stem-like cells to myocardial scar formation. Ryzhov S, Sung BH, Zhang Q, Weaver A, Gumina RJ, Biaggioni I, Feoktistov I (2014) Purinergic Signal 10(3): 477-86
    › Primary publication · 24584483 (PubMed) · PMC4152448 (PubMed Central)
  22. Exosome secretion is enhanced by invadopodia and drives invasive behavior. Hoshino D, Kirkbride KC, Costello K, Clark ES, Sinha S, Grega-Larson N, Tyska MJ, Weaver AM (2013) Cell Rep 5(5): 1159-68
    › Primary publication · 24290760 (PubMed) · PMC3873329 (PubMed Central)
  23. Synthetic and tissue-derived models for studying rigidity effects on invadopodia activity. Weaver AM, Page JM, Guelcher SA, Parekh A (2013) Methods Mol Biol : 171-89
    › Primary publication · 23868588 (PubMed)
  24. WAVE2 regulates epithelial morphology and cadherin isoform switching through regulation of Twist and Abl. Bryce NS, Reynolds AB, Koleske AJ, Weaver AM (2013) PLoS One 8(5): e64533
    › Primary publication · 23691243 (PubMed) · PMC3654908 (PubMed Central)
  25. Cell-cell fusion: a new function for invadosomes. Sung BH, Weaver A (2011) Curr Biol 21(3): R121-3
    › Primary publication · 21300277 (PubMed) · PMC3596881 (PubMed Central)