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Molecular and Cellular Biology

Houston, Texas

Image 1: Ovulated mouse cumulus cell oocyte complex immunostained for matrix proteins hyaluronan and versican. By JoAnne Richards, Ph.D.; Image 2: By Yi LI, Ph.D.; Image 3: Mouse oocyte at meiosis I immunostained  for tubulin (red) phosphop38MAPK (green) and DNA (blue). By JoAnne Richards,  Ph.D.;  Image 4: Expanded cumulus cell ooctye ocmplex  immunostained for hyaluronan (red), TSG6 (green) and DAN (blue). By JoAnne  Richards, Ph.D.;  Image 5: Epithelial cells taken from a mouse  mammary gland were cultured in a dish and transduced with a retrovirus  expressing two genes. The green staining shows green fluorescent protein and the red  staining shows progesterone receptor expression. The nucleus of each cell is  stained blue. Photomicrograph taken at 200X magnification.  By Sandra L. Grimm,  Ph.D.; Image 6: Ovarian vasculature (red) is excluded from the granulosa cells (blue) within growing follicles (round structures); Image 7:  Ovulated mouse cumulus cell oocyte  complex immunostained for matrix proteins hyaluronan and versican. By JoAnne Richards, Ph.D.
Department of Molecular and Cellular Biology
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Weiwen Long, Ph.D.

Weiwen Long, Ph.D. photoAssistant Professor
Department of Molecular and Cellular Biology

Education

Ph.D.: Tulane University, New Orleans
Postdoctoral training: Baylor College of Medicine, Houston

Research Interest

The Interplay between Steroid Receptor Coactivators and Protein Kinases in Cancer
My research interests and expertise have been directed to the fields of growth factor signaling, steroid receptor/coactivator signaling, and the interplay between these two signaling pathways in cancer progression and metastasis. Our current research interests/projects include:

1. Role of SRC-3∆4 in anti-hormone resistant breast and prostate cancer progression and metastasis. Cross-talk between protein kinase signaling and hormone receptor signaling (including genomic and non-genomic actions) confers anti-hormone resistance and tumor invasiveness in breast and prostate cancers. Interestingly, we have found that SRC-3∆4, a splice isoform of oncogenic steroid receptor coactivator 3 (SRC-3), not only acts as a signaling adaptor to meditate EGF signal transduction, but forms a complex with ERα (or androgen receptor), PI3K, and c-Src kinase in response to E2 (or androgen) stimulation. These findings suggest that SRC-3∆4 may mediate the cross-talk between growth factor signaling and steroid receptor signaling to promote anti-hormone resistance and tumor invasiveness in breast and/or prostate cancer. To test this possibility, two major projects are being pursued. The first is to define the role of SRC-3Δ4 in castration-resistant prostate cancer progression and to identify the underlying mechanisms of how SRC-3Δ4 co-activates AR in an androgen-independent manner. The second project is to investigate whether SRC-3∆4 integrates E2 non-genomic and genomic actions to promote breast cancer progression and elicit anti-estrogen resistance.

2. ERK3 signaling in cancer progression and metastasis. Extracellular signal-regulated kinase 3 (ERK3) is a member of the atypical MAP kinase subfamily. Unlike ERK1 and ERK2 that have been studied extensively, little is known about the upstream stimuli and activators of ERK3 or its downstream targets. The function of ERK3 in cancer development and progression is virtually unknown. We recently identified a novel function of ERK3 in promoting cancer cell invasiveness by phosphorylating SRC-3 and regulating its proinvasive activity. We will continue to identify the upstream activators, regulators, and the downstream effectors (targets) of ERK3 signaling by IP-MS analyses and the subsequent functional studies. In addition, we are generating and will utilize these in vivo animal models (conditional ERK3 knock-in and/or knock-out) to elucidate the roles of ERK3 signaling in caner progression and metastasis.

Contact Information

Baylor College of Medicine
One Baylor Plaza,
Houston, TX 77030

Phone: 713-798-8705
E-mail: wlong@bcm.edu

Selected Publications

  1. Long W, Foulds C, Qin J, Ding C, Lonard DM, Tsai S, Tsai M-J, O’Malley BW. Regulation of SRC-3 proinvasive activity by ERK3-mediated phosphorylation in lung cancer cells (Molecular Cell, in review).
  2. Hartig SM, He B, Long W, Buehrer BM, Mancini MA. (2011). Homeostatic levels of SRC-2 and SRC-3 promote early human adipogenesis. Journal of Cell Biology, 192(1):55-67. PMID: 21220509.
  3. Long W, Yi P, Amazit L, LaMarca HL, Ashcroft F, Kumar R, Mancini MA, Tsai SY, Tsai MJ, O'Malley BW. (2010). SRC-3∆4 mediates the interaction of EGFR with FAK to promote cell migration. Molecular Cell, 37(3):321-32. PMID: 20159552.
  4. Long W, O’Malley BW. (2010). Cross-talk among nuclear receptor coactivators and a membrane receptor promotes tumor cell growth and migration. Cell Cycle, 9(12):2269-2270. PMID: 20519947.
  5. Foulds CE, Tsimelzon A, Long W, Le A, Tsai SY, Tsai MJ, O'Malley BW. (2010). Expression profiling reveals unexpected targets and functions of the human steroid receptor RNA activator (SRA) gene. Molecular Endocrinology, 24:1090-105. PMID: 20219889.
  6. Li X, Amazit L, Long W, Lonard DM, Monaco JJ, O'Malley BW. (2007). Ubiquitin- and ATP-Independent Proteolytic Turnover of p21 by the REGγ-Proteasome Pathway. Molecular Cell, 26:831-842. PMID: 17588518.
  7. Naresh A*, Long W*, Vidal GA*, Wimley WC, Marrero L, Sartor CI, Tovey S, Cooke TG, Bartlett JM, Jones FE. (2006). The ERBB4/HER4 intracellular domain 4ICD is a BH3-only protein promoting apoptosis of breast cancer cells. Cancer Research, 66(12):6412-20. (*: co-first author). PMID: 16778220.
  8. Long W, Wagner KU, Lloyd KC, Binart N, Shillingford JM, Hennighausen L, Jones FE. (2003). Impaired differentiation and lactational failure of ERBB4-deficient mammary glands identify ERBB4 as an obligate mediator of STAT5. Development, 130(21):5257-68. PMID: 12954715.
  9. Clark DE, Williams CC, Duplessis TT, Moring KL, Notwick AR, Long W, Lane WS, Beuvink I, Hynes NE, Jones FE. (2005). ERBB4/HER4 potentiates STAT5A transcriptional activity by regulating novel STAT5A serine phosphorylation events. Journal of Biological Chemistry, 280(25):24175-80. PMID: 15863494.
  10. Li L, Cleary S, Long W, Mandarano MA, Birchmeier C, and Jones EF. (2002). The breast proto-oncogene, HRG alpha regulates epithelial proliferation and lobuloalveolar functional development in the mouse mammary gland. Oncogene, 21:4900-4907. PMID: 12118369.

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