Yabin Cheng, Guangdi Chen, Magdalena Martinka, Vincent Ho, Gang Li 

Slides:



Advertisements
Similar presentations
Nan-Hyung Kim, Ai-Young Lee  Journal of Investigative Dermatology 
Advertisements

RanBP3 Regulates Melanoma Cell Proliferation via Selective Control of Nuclear Export  Gaurav Pathria, Bhavuk Garg, Christine Wagner, Kanika Garg, Melanie.
Cell Surface CD74–MIF Interactions Drive Melanoma Survival in Response to Interferon-γ  Keiji Tanese, Yuuri Hashimoto, Zuzana Berkova, Yuling Wang, Felipe.
A Signal Transduction Pathway from TGF-β1 to SKP2 via Akt1 and c-Myc and its Correlation with Progression in Human Melanoma  Xuan Qu, Liangliang Shen,
IMP-3 Promotes Migration and Invasion of Melanoma Cells by Modulating the Expression of HMGA2 and Predicts Poor Prognosis in Melanoma  Yi-Shuan Sheen,
SECTM1 Produced by Tumor Cells Attracts Human Monocytes via CD7-Mediated Activation of the PI3K Pathway  Tao Wang, Yingbin Ge, Min Xiao, Alfonso Lopez-Coral,
MicroRNA-31 Promotes Skin Wound Healing by Enhancing Keratinocyte Proliferation and Migration  Dongqing Li, X.I. Li, Aoxue Wang, Florian Meisgen, Andor.
Glutamine Suppresses DNFB-Induced Contact Dermatitis by Deactivating p38 Mitogen– Activated Protein Kinase via Induction of MAPK Phosphatase-1  Otgonzaya.
Cdc42 Inhibits ERK-Mediated Collagenase-1 (MMP-1) Expression in Collagen-Activated Human Keratinocytes  Maryam G. Rohani, Brian K. Pilcher, Peter Chen,
TWEAK/Fn14 Activation Contributes to the Pathogenesis of Bullous Pemphigoid  Yale Liu, Lingling Peng, Liang Li, Chengfei Liu, Xiao Hu, Shengxiang Xiao,
Critical Role of 5-Lipoxygenase and Heme Oxygenase-1 in Wound Healing
Yongping Shao, Kaitlyn Le, Hanyin Cheng, Andrew E. Aplin 
Cleidson P. Alves, Milene H. Moraes, Josane F. Sousa, Carmen Lucia S
Volume 33, Issue 2, Pages (January 2009)
RanBP3 Regulates Melanoma Cell Proliferation via Selective Control of Nuclear Export  Gaurav Pathria, Bhavuk Garg, Christine Wagner, Kanika Garg, Melanie.
Verena N. Lorenz, Michael P. Schön, Cornelia S. Seitz 
Complement Factor H: A Biomarker for Progression of Cutaneous Squamous Cell Carcinoma  Pilvi M. Riihilä, Liisa M. Nissinen, Risto Ala-aho, Markku Kallajoki,
CCN2 Expression by Tumor Stroma Is Required for Melanoma Metastasis
Glyoxalase I Is Differentially Expressed in Cutaneous Neoplasms and Contributes to the Progression of Squamous Cell Carcinoma  Xiao-Yan Zou, Dong Ding,
Melanoma Cell Invasiveness Is Promoted at Least in Part by the Epidermal Growth Factor–Like Repeats of Tenascin-C  Jelena Grahovac, Dorothea Becker, Alan.
EIF4E Is an Adverse Prognostic Marker of Melanoma Patient Survival by Increasing Melanoma Cell Invasion  Shahram Khosravi, Kevin J. Tam, Gholamreza S.
Ji-Young Kim, Tae-Ryong Lee, Ai-Young Lee 
Cadherin 11, a miR-675 Target, Induces N-Cadherin Expression and Epithelial– Mesenchymal Transition in Melasma  Nan-Hyung Kim, Soo-Hyun Choi, Tae Ryong.
Andreea M. Bujor, Jaspreet Pannu, Shizhong Bu, Edwin A. Smith, Robin C
Rolando Perez-Lorenzo, Kamraan Z. Gill, Che-Hung Shen, Feng X
P21-Activated Kinase 4 Critically Regulates Melanogenesis via Activation of the CREB/MITF and β-Catenin/MITF Pathways  Cheong-Yong Yun, Soon-Tae You,
Osteopontin Expression Correlates with Melanoma Invasion
Tumor-Derived Fibronectin Is Involved in Melanoma Cell Invasion and Regulated by V600E B-Raf Signaling Pathway  Cédric Gaggioli, Guillaume Robert, Corine.
IGF-II-Mediated COX-2 Gene Expression in Human Keratinocytes Through Extracellular Signal-Regulated Kinase Pathway  Hye Jung Kim, Tae-Yoon Kim  Journal.
Regulation of IL-33 Expression by IFN-γ and Tumor Necrosis Factor-α in Normal Human Epidermal Keratinocytes  Jitlada Meephansan, Hidetoshi Tsuda, Mayumi.
SIRT1 Regulates Lamellipodium Extension and Migration of Melanoma Cells  Risa Kunimoto, Kowichi Jimbow, Akihiko Tanimura, Masahiro Sato, Kouhei Horimoto,
Leon Raskin, Douglas R. Fullen, Thomas J. Giordano, Dafydd G
PDZK1 Upregulation in Estrogen-Related Hyperpigmentation in Melasma
Plexin B1 Suppresses c-Met in Melanoma: A Role for Plexin B1 as a Tumor-Suppressor Protein through Regulation of c-Met  Laurel Stevens, Lindy McClelland,
Prolonged Activation of ERK Contributes to the Photorejuvenation Effect in Photodynamic Therapy in Human Dermal Fibroblasts  Yong Hyun Jang, Gi-Bang Koo,
Inhibition of CRM1-Mediated Nucleocytoplasmic Transport: Triggering Human Melanoma Cell Apoptosis by Perturbing Multiple Cellular Pathways  Gaurav Pathria,
Collagen XVII Participates in Keratinocyte Adhesion to Collagen IV, and in p38MAPK- Dependent Migration and Cell Signaling  Hongjiang Qiao, Akihiko Shibaki,
Sema4D, the Ligand for Plexin B1, Suppresses c-Met Activation and Migration and Promotes Melanocyte Survival and Growth  Joanne Soong, Yulin Chen, Elina.
Human Mitochondrial NAD(P)+–Dependent Malic Enzyme Participates in Cutaneous Melanoma Progression and Invasion  Yung-Lung Chang, Hong-Wei Gao, Chien-Ping.
Wnt5A Activates the Calpain-Mediated Cleavage of Filamin A
Profiling Motility Signal-Specific Genes in Primary Human Keratinocytes  Chieh-Fang Cheng, Jianhua Fan, Balaji Bandyopahdhay, Dennis Mock, Shengxi Guan,
GSK3β Inhibition Blocks Melanoma Cell/Host Interactions by Downregulating N- Cadherin Expression and Decreasing FAK Phosphorylation  Jobin K. John, Kim.
Nucleus Accumbens-Associated 1 Contributes to Cortactin Deacetylation and Augments the Migration of Melanoma Cells  Kanako Tsunoda, Hiroki Oikawa, Hiroshi.
Kellie J. White, Vincent J. Maffei, Marvin Newton-West, Robert A
CD63 Tetraspanin Is a Negative Driver of Epithelial-to-Mesenchymal Transition in Human Melanoma Cells  Antonella Lupia, Silvia Peppicelli, Ewa Witort,
Reduced Expression of Connective Tissue Growth Factor (CTGF/CCN2) Mediates Collagen Loss in Chronologically Aged Human Skin  TaiHao Quan, Yuan Shao, Tianyuan.
Chi-Hyun Park, Youngji Moon, Chung Min Shin, Jin Ho Chung 
SIRT1, a Class III Histone Deacetylase, Regulates LPS-Induced Inflammation in Human Keratinocytes and Mediates the Anti-Inflammatory Effects of Hinokitiol 
YAP and TAZ Regulate Skin Wound Healing
Bim Expression Is Reduced in Human Cutaneous Melanomas
Critical Role of Paxillin in Aging of Human Skin
Insulin-Like Growth Factor-Binding Protein 7 Regulates Keratinocyte Proliferation, Differentiation and Apoptosis  Janna Nousbeck, Ofer Sarig, Nili Avidan,
TWEAK/Fn14 Activation Contributes to the Pathogenesis of Bullous Pemphigoid  Yale Liu, Lingling Peng, Liang Li, Chengfei Liu, Xiao Hu, Shengxiang Xiao,
Collagen Synthesis Is Suppressed in Dermal Fibroblasts by the Human Antimicrobial Peptide LL-37  Hyun Jeong Park, Dae Ho Cho, Hee Jung Kim, Jun Young.
Alexandra V. Lucs, Allan L. Abramson, Bettie M. Steinberg 
HGF-Promoted Motility in Primary Human Melanocytes Depends on CD44v6 Regulated via NF-kappa B, Egr-1, and C/EBP-beta  Sabine Damm, Petra Koefinger, Martina.
Macrophage Inhibitory Cytokine-1 Is Overexpressed in Malignant Melanoma and Is Associated with Tumorigenicity  Glen M. Boyle, Julie Pedley, Adam C. Martyn,
Anna Flammiger, Robert Besch, Anthony L. Cook, Tanja Maier, Richard A
Nan-Hyung Kim, Ai-Young Lee  Journal of Investigative Dermatology 
Loss of Class III β-Tubulin Induced by Histone Deacetylation Is Associated with Chemosensitivity to Paclitaxel in Malignant Melanoma Cells  Kiyomi Akasaka,
Madhuri Bhandaru, Magdalena Martinka, Gang Li, Anand Rotte 
IL-17A Upregulates Keratin 17 Expression in Keratinocytes through STAT1- and STAT3- Dependent Mechanisms  Xiaowei Shi, Liang Jin, Erle Dang, Ting Chang,
Transient Receptor Potential Vanilloid-1 Mediates Heat-Shock-Induced Matrix Metalloproteinase-1 Expression in Human Epidermal Keratinocytes  Wen H. Li,
Nan-Lin Wu, Te-An Lee, Te-Lung Tsai, Wan-Wan Lin 
Expression of Matrix Metalloproteinase-13 Is Controlled by IL-13 via PI3K/Akt3 and PKC-δ in Normal Human Dermal Fibroblasts  Chikako Moriya, Masatoshi.
Plexin C1, A Receptor for Semaphorin 7A, Inactivates Cofilin and Is a Potential Tumor Suppressor for Melanoma Progression  Glynis A. Scott, Lindy A. McClelland,
Deon G. Uffort, Elizabeth A. Grimm, Julie A. Ellerhorst 
P21-Activated Kinase 4 Critically Regulates Melanogenesis via Activation of the CREB/MITF and β-Catenin/MITF Pathways  Cheong-Yong Yun, Soon-Tae You,
Role and Regulation of STAT3 Phosphorylation at Ser727 in Melanocytes and Melanoma Cells  Masanobu Sakaguchi, Masahiro Oka, Tetsushi Iwasaki, Yasuo Fukami,
B7-H3 Associated with Tumor Progression and Epigenetic Regulatory Activity in Cutaneous Melanoma  Jinhua Wang, Kelly K. Chong, Yoshitaka Nakamura, Linhda.
Presentation transcript:

Prognostic Significance of Fbw7 in Human Melanoma and Its Role in Cell Migration  Yabin Cheng, Guangdi Chen, Magdalena Martinka, Vincent Ho, Gang Li  Journal of Investigative Dermatology  Volume 133, Issue 7, Pages 1794-1802 (July 2013) DOI: 10.1038/jid.2013.58 Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 1 Fbw7 expression is reduced in human advanced melanoma. (a–d) Representative images of Fbw7 immunohistochemical staining in human melanoma TMA. (a, c) Normal nevus with positive staining. Arrows indicate positive Fbw7 nuclear staining. (b, d) Metastatic melanoma with negative staining. (a, b) Bar=40μm; (c, d) bar=10μm. (e) Reduced Fbw7 expression correlates with melanoma progression. DN, dysplastic nevi; Fbw7, F-box and WD repeat domain-containing 7; MM, metastatic melanoma; NN, normal nevi; PM, primary melanoma; TMA, tissue microarray. *P<0.05, **P<0.01. Journal of Investigative Dermatology 2013 133, 1794-1802DOI: (10.1038/jid.2013.58) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 2 Kaplan–Meier survival analyses of melanoma patients. Patients with negative Fbw7 (F-box and WD repeat domain-containing 7) expression have a significantly worse (a) overall and (b) disease-specific 5-year survival than those with positive Fbw7 expression (P=0.037 and 0.015, respectively, log-rank test). Journal of Investigative Dermatology 2013 133, 1794-1802DOI: (10.1038/jid.2013.58) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 3 Fbw7 (F-box and WD repeat domain-containing 7) mRNA expression in normal melanocytes and melanoma cell lines. (a) Fbw7α protein expression level was reduced in melanoma cell lines as compared with normal melanocytes. (b) Total Fbw7 mRNA level was reduced in melanoma cell lines as compared with melanocytes. (c) Comparison of mRNA expression of three Fbw7 isoforms in melanocytes and melanoma cell lines. Journal of Investigative Dermatology 2013 133, 1794-1802DOI: (10.1038/jid.2013.58) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 4 Enforced Fbw7α (F-box and WD repeat domain-containing 7) expression inhibits melanoma cell migration. (a) Representative images of the effects of Fbw7α overexpression on melanoma cell migration. (b) The inhibition of Fbw7α on melanoma cell migration was quantified by counting the migrated cells in five random fields of each well; error bars equal to means±SD. The data were obtained from three independent experiments. **P<0.01. (c) Western blot analysis of Fbw7α expression, total extracellular signal–regulated kinase 1/2 (ERK1/2), and phosphorylated ERK1/2 (p-ERK1/2). Journal of Investigative Dermatology 2013 133, 1794-1802DOI: (10.1038/jid.2013.58) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 5 Treatment with selective MEK (MAPK/ERK kinase) inhibitor, PD98059, abolished Fbw7α (F-box and WD repeat domain-containing 7) knockdown–induced melanoma cell migration. (a) Representative images show the effects of PD98059 on melanoma cell migration. After Fbw7α knockdown, MMRU cells were treated with 80μM PD98059 for 24hours in serum-free medium, and then the wound-healing assay was performed. (b) Quantification of a. The induction of Fbw7α knockdown on melanoma cell migration was quantified by counting the migrated cells in five random fields of each well; error bars equal to means±SD. Data were obtained from three independent experiments. ***P<0.001. (c) Western blot analysis showed efficient Fbw7α knockdown using two small interfering RNAs (siRNAs). (d) Western blot analysis of extracellular signal–regulated kinase 1/2 (ERK1/2) phosphorylation (p-ERK1/2) by MEK inhibitor PD98059. Journal of Investigative Dermatology 2013 133, 1794-1802DOI: (10.1038/jid.2013.58) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions

Figure 6 Fbw7α (F-box and WD repeat domain-containing 7) affects RhoA activity and stress fiber formation. (a) Fbw7α-knockdown (KD)–induced RhoA activity was abolished by PD98059. MMRU cells transfected with siControl and siFbw7α small interfering RNAs (siRNAs) were serum starved for 24hours, and had serum stimulation for 30minutes. (b) Decreased stress fiber formation in Fbw7α-overexpressed MMRU cells. MMRU cells were transfected with FLAG-Fbw7α or vector control, followed by serum starvation for 24hours and serum stimulation for 30minutes. DAPI, 4',6-diamidino-2-phenylindole. (c) Increased stress fiber formation after Fbw7α-KD. MMRU cells were transfected with siControl and siFbw7α siRNAs, followed by serum starvation for 24hours and serum stimulation for 30minutes. For MEK (MAPK/ERK kinase) inhibitor treatment, MMRU cells were incubated with serum-free medium containing 80μM PD98059 for 24hours. Original magnification × 630. (d) Quantification of b and c. Relative intensity of F-actin was examined by ImageJ software; **P<0.01, ***P<0.001. Journal of Investigative Dermatology 2013 133, 1794-1802DOI: (10.1038/jid.2013.58) Copyright © 2013 The Society for Investigative Dermatology, Inc Terms and Conditions