Rebecca Cook
Faculty Member
Last active: 2/12/2015

Profile

Many of the physiologic signaling pathways that contribute to tissue development and function are often comandeered by tumor cells to prmote their own growth and metastasis. It is becoming increasingly clear that signaling pathways necessary for growth of the breast epithelium during puberty and pregnancy, and for breast remodeling after lactation are abnormally activated during various stages of tumor formation and progression. The long-term goal of our research is a greater understanding of these signaling pathways, and how they contribute to both mammary gland physiology and breast cancer.

Much of our research focuses on signaling pathways induced by the ErbB family of receptor tyrosine kinases, which include EGFR, ErbB2, ErbB3, and ErbB4. Evidence suggests that three of these family members, EGFR, ErbB2, and ErbB3, are required for increased growth of the mammary epithelium during puberty and pregnancy. Their pathologic overexpression contributes to breast tumor formation and increased malignancy. Much of our current research examines the specific contributions of ErbB3 to breast cancer progression, and its potential as a therapeutic target in ErbB2-expressing breast cancers.

In contrast, ErbB4 is required for lactational differentiation of the mammary epithelium. The role and prognostic value of ErbB4 in breast cancer remains unclear, and our recently published work is aimed at understanding how ErbB4 expression impacts the behavior of normal mammary epithelial cells. Future studies will build on this work and focus on how ErbB4, and the signaling pathways activated in response to ErbB4, impact growth and progression of mammary tumors.

Finally, remodeling of the mammary gland after lactation ceases, a process known as involution, is a complex process that requires elimination of much of the mammary epithelium, accompanied by a profound level of structural remodling of the mammary stroma. Remodeling of the mammary stroma requires a series of communications between the mammary epithelium and its surrounding stromal environment. Evidence suggests that many of the stromal remodeling events and the signaling pathways that regulate these events are also active in breast tumors, and contribute to the pathology of the disease. Our ongoing research will use models of impaired involution versus sustained involution to determine the impact of involution-specific stromal remodeling events upon homeostasis of the mammary epithelium, and to the growth and metastasis of breast tumors.

Publications

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

Featured publications are shown below:

  1. Receptor tyrosine kinase ERBB4 mediates acquired resistance to ERBB2 inhibitors in breast cancer cells. Canfield K, Li J, Wilkins OM, Morrison MM, Ung M, Wells W, Williams CR, Liby KT, Vullhorst D, Buonanno A, Hu H, Schiff R, Cook RS, Kurokawa M (2015) Cell Cycle 14(4): 648-55
    › Primary publication · 25590338 (PubMed) · PMC4614407 (PubMed Central)
  2. Efferocytosis produces a prometastatic landscape during postpartum mammary gland involution. Stanford JC, Young C, Hicks D, Owens P, Williams A, Vaught DB, Morrison MM, Lim J, Williams M, Brantley-Sieders DM, Balko JM, Tonetti D, Earp HS, Cook RS (2014) J Clin Invest 124(11): 4737-52
    › Primary publication · 25250573 (PubMed) · PMC4347249 (PubMed Central)
  3. Quantitative optical imaging of primary tumor organoid metabolism predicts drug response in breast cancer. Walsh AJ, Cook RS, Sanders ME, Aurisicchio L, Ciliberto G, Arteaga CL, Skala MC (2014) Cancer Res 74(18): 5184-94
    › Primary publication · 25100563 (PubMed) · PMC4167558 (PubMed Central)
  4. In vivo hyperspectral imaging of microvessel response to trastuzumab treatment in breast cancer xenografts. McCormack DR, Walsh AJ, Sit W, Arteaga CL, Chen J, Cook RS, Skala MC (2014) Biomed Opt Express 5(7): 2247-61
    › Primary publication · 25071962 (PubMed) · PMC4102362 (PubMed Central)
  5. Genetic and pharmacologic inhibition of EPHA2 promotes apoptosis in NSCLC. Amato KR, Wang S, Hastings AK, Youngblood VM, Santapuram PR, Chen H, Cates JM, Colvin DC, Ye F, Brantley-Sieders DM, Cook RS, Tan L, Gray NS, Chen J (2014) J Clin Invest 124(5): 2037-49
    › Primary publication · 24713656 (PubMed) · PMC4001547 (PubMed Central)
  6. CXCR4 drives the metastatic phenotype in breast cancer through induction of CXCR2 and activation of MEK and PI3K pathways. Sobolik T, Su YJ, Wells S, Ayers GD, Cook RS, Richmond A (2014) Mol Biol Cell 25(5): 566-82
    › Primary publication · 24403602 (PubMed) · PMC3937084 (PubMed Central)
  7. Molecular profiling of the residual disease of triple-negative breast cancers after neoadjuvant chemotherapy identifies actionable therapeutic targets. Balko JM, Giltnane JM, Wang K, Schwarz LJ, Young CD, Cook RS, Owens P, Sanders ME, Kuba MG, Sánchez V, Kurupi R, Moore PD, Pinto JA, Doimi FD, Gómez H, Horiuchi D, Goga A, Lehmann BD, Bauer JA, Pietenpol JA, Ross JS, Palmer GA, Yelensky R, Cronin M, Miller VA, Stephens PJ, Arteaga CL (2014) Cancer Discov 4(2): 232-45
    › Primary publication · 24356096 (PubMed) · PMC3946308 (PubMed Central)
  8. Mouse models and anti-HER2 therapies. Hanker AB, Cook RS, Arteaga CL (2013) Oncotarget 4(11): 1866-7
    › Primary publication · 24272818 (PubMed) · PMC3875754 (PubMed Central)
  9. Optical metabolic imaging identifies glycolytic levels, subtypes, and early-treatment response in breast cancer. Walsh AJ, Cook RS, Manning HC, Hicks DJ, Lafontant A, Arteaga CL, Skala MC (2013) Cancer Res 73(20): 6164-74
    › Primary publication · 24130112 (PubMed) · PMC3801432 (PubMed Central)
  10. ErbB3 downregulation enhances luminal breast tumor response to antiestrogens. Morrison MM, Hutchinson K, Williams MM, Stanford JC, Balko JM, Young C, Kuba MG, Sánchez V, Williams AJ, Hicks DJ, Arteaga CL, Prat A, Perou CM, Earp HS, Massarweh S, Cook RS (2013) J Clin Invest 123(10): 4329-43
    › Primary publication · 23999432 (PubMed) · PMC3784526 (PubMed Central)
  11. Activation of MAPK pathways due to DUSP4 loss promotes cancer stem cell-like phenotypes in basal-like breast cancer. Balko JM, Schwarz LJ, Bhola NE, Kurupi R, Owens P, Miller TW, Gómez H, Cook RS, Arteaga CL (2013) Cancer Res 73(20): 6346-58
    › Primary publication · 23966295 (PubMed) · PMC4090144 (PubMed Central)
  12. Mutant PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies. Hanker AB, Pfefferle AD, Balko JM, Kuba MG, Young CD, Sánchez V, Sutton CR, Cheng H, Perou CM, Zhao JJ, Cook RS, Arteaga CL (2013) Proc Natl Acad Sci U S A 110(35): 14372-7
    › Primary publication · 23940356 (PubMed) · PMC3761610 (PubMed Central)
  13. MerTK inhibition in tumor leukocytes decreases tumor growth and metastasis. Cook RS, Jacobsen KM, Wofford AM, DeRyckere D, Stanford J, Prieto AL, Redente E, Sandahl M, Hunter DM, Strunk KE, Graham DK, Earp HS (2013) J Clin Invest 123(8): 3231-42
    › Primary publication · 23867499 (PubMed) · PMC3726162 (PubMed Central)
  14. Conditional loss of ErbB3 delays mammary gland hyperplasia induced by mutant PIK3CA without affecting mammary tumor latency, gene expression, or signaling. Young CD, Pfefferle AD, Owens P, Kuba MG, Rexer BN, Balko JM, Sánchez V, Cheng H, Perou CM, Zhao JJ, Cook RS, Arteaga CL (2013) Cancer Res 73(13): 4075-85
    › Primary publication · 23633485 (PubMed) · PMC3702683 (PubMed Central)
  15. TGF-β inhibition enhances chemotherapy action against triple-negative breast cancer. Bhola NE, Balko JM, Dugger TC, Kuba MG, Sánchez V, Sanders M, Stanford J, Cook RS, Arteaga CL (2013) J Clin Invest 123(3): 1348-58
    › Primary publication · 23391723 (PubMed) · PMC3582135 (PubMed Central)
  16. Dual blockade of HER2 in HER2-overexpressing tumor cells does not completely eliminate HER3 function. Garrett JT, Sutton CR, Kuba MG, Cook RS, Arteaga CL (2013) Clin Cancer Res 19(3): 610-9
    › Primary publication · 23224399 (PubMed) · PMC3563762 (PubMed Central)
  17. Local breast cancer spatial patterning: a tool for community health resource allocation to address local disparities in breast cancer mortality. Brantley-Sieders DM, Fan KH, Deming-Halverson SL, Shyr Y, Cook RS (2012) PLoS One 7(9): e45238
    › Primary publication · 23028869 (PubMed) · PMC3460936 (PubMed Central)
  18. Targeting BRCA1 localization to augment breast tumor sensitivity to poly(ADP-Ribose) polymerase inhibition. Yang ES, Nowsheen S, Rahman MA, Cook RS, Xia F (2012) Cancer Res 72(21): 5547-55
    › Primary publication · 22962264 (PubMed) · PMC3771348 (PubMed Central)
  19. Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance. Balko JM, Cook RS, Vaught DB, Kuba MG, Miller TW, Bhola NE, Sanders ME, Granja-Ingram NM, Smith JJ, Meszoely IM, Salter J, Dowsett M, Stemke-Hale K, González-Angulo AM, Mills GB, Pinto JA, Gómez HL, Arteaga CL (2012) Nat Med 18(7): 1052-9
    › Primary publication · 22683778 (PubMed) · PMC3693569 (PubMed Central)
  20. HER3 is required for HER2-induced preneoplastic changes to the breast epithelium and tumor formation. Vaught DB, Stanford JC, Young C, Hicks DJ, Wheeler F, Rinehart C, Sánchez V, Koland J, Muller WJ, Arteaga CL, Cook RS (2012) Cancer Res 72(10): 2672-82
    › Primary publication · 22461506 (PubMed) · PMC3693553 (PubMed Central)
  21. Optical imaging of metabolism in HER2 overexpressing breast cancer cells. Walsh A, Cook RS, Rexer B, Arteaga CL, Skala MC (2012) Biomed Opt Express 3(1): 75-85
    › Primary publication · 22254170 (PubMed) · PMC3255344 (PubMed Central)
  22. The receptor tyrosine kinase ErbB3 maintains the balance between luminal and basal breast epithelium. Balko JM, Miller TW, Morrison MM, Hutchinson K, Young C, Rinehart C, Sánchez V, Jee D, Polyak K, Prat A, Perou CM, Arteaga CL, Cook RS (2012) Proc Natl Acad Sci U S A 109(1): 221-6
    › Primary publication · 22178756 (PubMed) · PMC3252958 (PubMed Central)
  23. ErbB3 ablation impairs PI3K/Akt-dependent mammary tumorigenesis. Cook RS, Garrett JT, Sánchez V, Stanford JC, Young C, Chakrabarty A, Rinehart C, Zhang Y, Wu Y, Greenberger L, Horak ID, Arteaga CL (2011) Cancer Res 71(11): 3941-51
    › Primary publication · 21482676 (PubMed) · PMC3204389 (PubMed Central)
  24. Transcriptional and posttranslational up-regulation of HER3 (ErbB3) compensates for inhibition of the HER2 tyrosine kinase. Garrett JT, Olivares MG, Rinehart C, Granja-Ingram ND, Sánchez V, Chakrabarty A, Dave B, Cook RS, Pao W, McKinely E, Manning HC, Chang J, Arteaga CL (2011) Proc Natl Acad Sci U S A 108(12): 5021-6
    › Primary publication · 21385943 (PubMed) · PMC3064360 (PubMed Central)
  25. Epithelial cell-directed efferocytosis in the post-partum mammary gland is necessary for tissue homeostasis and future lactation. Sandahl M, Hunter DM, Strunk KE, Earp HS, Cook RS (2010) BMC Dev Biol : 122
    › Primary publication · 21192804 (PubMed) · PMC3022573 (PubMed Central)
  26. Cooperative signaling between Slit2 and Ephrin-A1 regulates a balance between angiogenesis and angiostasis. Dunaway CM, Hwang Y, Lindsley CW, Cook RS, Wu JY, Boothby M, Chen J, Brantley-Sieders DM (2011) Mol Cell Biol 31(3): 404-16
    › Primary publication · 21135133 (PubMed) · PMC3028625 (PubMed Central)
  27. H1047R phosphatidylinositol 3-kinase mutant enhances HER2-mediated transformation by heregulin production and activation of HER3. Chakrabarty A, Rexer BN, Wang SE, Cook RS, Engelman JA, Arteaga CL (2010) Oncogene 29(37): 5193-203
    › Primary publication · 20581867 (PubMed) · PMC2945381 (PubMed Central)
  28. Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its activation. Mahajan K, Coppola D, Challa S, Fang B, Chen YA, Zhu W, Lopez AS, Koomen J, Engelman RW, Rivera C, Muraoka-Cook RS, Cheng JQ, Schönbrunn E, Sebti SM, Earp HS, Mahajan NP (2010) PLoS One 5(3): e9646
    › Primary publication · 20333297 (PubMed) · PMC2841635 (PubMed Central)
  29. Elevation of receptor tyrosine kinase EphA2 mediates resistance to trastuzumab therapy. Zhuang G, Brantley-Sieders DM, Vaught D, Yu J, Xie L, Wells S, Jackson D, Muraoka-Cook R, Arteaga C, Chen J (2010) Cancer Res 70(1): 299-308
    › Primary publication · 20028874 (PubMed) · PMC3859619 (PubMed Central)
  30. Inhibition of mammalian target of rapamycin is required for optimal antitumor effect of HER2 inhibitors against HER2-overexpressing cancer cells. Miller TW, Forbes JT, Shah C, Wyatt SK, Manning HC, Olivares MG, Sanchez V, Dugger TC, de Matos Granja N, Narasanna A, Cook RS, Kennedy JP, Lindsley CW, Arteaga CL (2009) Clin Cancer Res 15(23): 7266-76
    › Primary publication · 19934303 (PubMed) · PMC2787848 (PubMed Central)
  31. ErbB4 splice variants Cyt1 and Cyt2 differ by 16 amino acids and exert opposing effects on the mammary epithelium in vivo. Muraoka-Cook RS, Sandahl MA, Strunk KE, Miraglia LC, Husted C, Hunter DM, Elenius K, Chodosh LA, Earp HS (2009) Mol Cell Biol 29(18): 4935-48
    › Primary publication · 19596786 (PubMed) · PMC2738276 (PubMed Central)
  32. The E3 ubiquitin ligase WWP1 selectively targets HER4 and its proteolytically derived signaling isoforms for degradation. Feng SM, Muraoka-Cook RS, Hunter D, Sandahl MA, Caskey LS, Miyazawa K, Atfi A, Earp HS (2009) Mol Cell Biol 29(3): 892-906
    › Primary publication · 19047365 (PubMed) · PMC2630679 (PubMed Central)
  33. Prolactin and ErbB4/HER4 signaling interact via Janus kinase 2 to induce mammary epithelial cell gene expression differentiation. Muraoka-Cook RS, Sandahl M, Hunter D, Miraglia L, Earp HS (2008) Mol Endocrinol 22(10): 2307-21
    › Primary publication · 18653779 (PubMed) · PMC2582536 (PubMed Central)
  34. ErbB4/HER4: role in mammary gland development, differentiation and growth inhibition. Muraoka-Cook RS, Feng SM, Strunk KE, Earp HS (2008) J Mammary Gland Biol Neoplasia 13(2): 235-46
    › Primary publication · 18437540 (PubMed) · PMC3325098 (PubMed Central)
  35. The receptor tyrosine kinase EphA2 promotes mammary adenocarcinoma tumorigenesis and metastatic progression in mice by amplifying ErbB2 signaling. Brantley-Sieders DM, Zhuang G, Hicks D, Fang WB, Hwang Y, Cates JM, Coffman K, Jackson D, Bruckheimer E, Muraoka-Cook RS, Chen J (2008) J Clin Invest 118(1): 64-78
    › Primary publication · 18079969 (PubMed) · PMC2129239 (PubMed Central)
  36. HER4 D-box sequences regulate mitotic progression and degradation of the nuclear HER4 cleavage product s80HER4. Strunk KE, Husted C, Miraglia LC, Sandahl M, Rearick WA, Hunter DM, Earp HS, Muraoka-Cook RS (2007) Cancer Res 67(14): 6582-90
    › Primary publication · 17638867 (PubMed) · PMC2917069 (PubMed Central)
  37. The HER4 cytoplasmic domain, but not its C terminus, inhibits mammary cell proliferation. Feng SM, Sartor CI, Hunter D, Zhou H, Yang X, Caskey LS, Dy R, Muraoka-Cook RS, Earp HS (2007) Mol Endocrinol 21(8): 1861-76
    › Primary publication · 17505063 (PubMed) · PMC2917064 (PubMed Central)
  38. Heregulin-dependent delay in mitotic progression requires HER4 and BRCA1. Muraoka-Cook RS, Caskey LS, Sandahl MA, Hunter DM, Husted C, Strunk KE, Sartor CI, Rearick WA, McCall W, Sgagias MK, Cowan KH, Earp HS (2006) Mol Cell Biol 26(17): 6412-24
    › Primary publication · 16914727 (PubMed) · PMC1592831 (PubMed Central)
  39. The intracellular domain of ErbB4 induces differentiation of mammary epithelial cells. Muraoka-Cook RS, Sandahl M, Husted C, Hunter D, Miraglia L, Feng SM, Elenius K, Earp HS (2006) Mol Biol Cell 17(9): 4118-29
    › Primary publication · 16837552 (PubMed) · PMC1556387 (PubMed Central)
  40. Activated type I TGFbeta receptor kinase enhances the survival of mammary epithelial cells and accelerates tumor progression. Muraoka-Cook RS, Shin I, Yi JY, Easterly E, Barcellos-Hoff MH, Yingling JM, Zent R, Arteaga CL (2006) Oncogene 25(24): 3408-23
    › Primary publication · 16186809 (PubMed)
  41. Dual role of transforming growth factor beta in mammary tumorigenesis and metastatic progression. Muraoka-Cook RS, Dumont N, Arteaga CL (2005) Clin Cancer Res 11(2 Pt 2): 937s-43s
    › Primary publication · 15701890 (PubMed)
  42. Conditional overexpression of active transforming growth factor beta1 in vivo accelerates metastases of transgenic mammary tumors. Muraoka-Cook RS, Kurokawa H, Koh Y, Forbes JT, Roebuck LR, Barcellos-Hoff MH, Moody SE, Chodosh LA, Arteaga CL (2004) Cancer Res 64(24): 9002-11
    › Primary publication · 15604265 (PubMed)
  43. Increased malignancy of Neu-induced mammary tumors overexpressing active transforming growth factor beta1. Muraoka RS, Koh Y, Roebuck LR, Sanders ME, Brantley-Sieders D, Gorska AE, Moses HL, Arteaga CL (2003) Mol Cell Biol 23(23): 8691-703
    › Primary publication · 14612410 (PubMed) · PMC262670 (PubMed Central)
  44. Blockade of TGF-beta inhibits mammary tumor cell viability, migration, and metastases. Muraoka RS, Dumont N, Ritter CA, Dugger TC, Brantley DM, Chen J, Easterly E, Roebuck LR, Ryan S, Gotwals PJ, Koteliansky V, Arteaga CL (2002) J Clin Invest 109(12): 1551-9
    › Primary publication · 12070302 (PubMed) · PMC151012 (PubMed Central)
  45. ErbB2/Neu-induced, cyclin D1-dependent transformation is accelerated in p27-haploinsufficient mammary epithelial cells but impaired in p27-null cells. Muraoka RS, Lenferink AE, Law B, Hamilton E, Brantley DM, Roebuck LR, Arteaga CL (2002) Mol Cell Biol 22(7): 2204-19
    › Primary publication · 11884607 (PubMed) · PMC133673 (PubMed Central)
  46. Cyclin-dependent kinase inhibitor p27(Kip1) is required for mouse mammary gland morphogenesis and function. Muraoka RS, Lenferink AE, Simpson J, Brantley DM, Roebuck LR, Yakes FM, Arteaga CL (2001) J Cell Biol 153(5): 917-32
    › Primary publication · 11381079 (PubMed) · PMC2174338 (PubMed Central)
  47. Characterization of the mouse Ron/Stk receptor tyrosine kinase gene. Waltz SE, Toms CL, McDowell SA, Clay LA, Muraoka RS, Air EL, Sun WY, Thomas MB, Degen SJ (1998) Oncogene 16(1): 27-42
    › Primary publication · 9467940 (PubMed)
  48. Functional characterization of domains contained in hepatocyte growth factor-like protein. Waltz SE, McDowell SA, Muraoka RS, Air EL, Flick LM, Chen YQ, Wang MH, Degen SJ (1997) J Biol Chem 272(48): 30526-37
    › Primary publication · 9374547 (PubMed)