Notch is a highly conserved transmembrane receptor that determines cell fate. Notch signaling denotes cleavage of the Notch intracellular domain, its translocation to the nucleus, and subsequent activation of target gene transcription. Involvement of Notch signaling in several cancers is well known, but its role in melanoma remains poorly characterized. Here we show that the Notch1 pathway is activated in human melanoma. Blocking Notch signaling suppressed whereas constitutive activation of the Notch1 pathway enhanced primary melanoma cell growth both in vitro and in vivo yet had little effect on metastatic melanoma cells. Activation of Notch1 signaling enabled primary melanoma cells to gain metastatic capability. Furthermore, the oncogenic effect of Notch1 on primary melanoma cells was mediated by β-catenin, which was upregulated following Notch1 activation. Inhibiting β-catenin expression reversed Notch1-enhanced tumor growth and metastasis. Our data therefore suggest a β-catenin–dependent, stage-specific role for Notch1 signaling in promoting the progression of primary melanoma.
Klara Balint, Min Xiao, Chelsea C. Pinnix, Akinobu Soma, Imre Veres, Istvan Juhasz, Eric J. Brown, Anthony J. Capobianco, Meenhard Herlyn, Zhao-Jun Liu
Title and authors | Publication | Year |
---|---|---|
Signal pathways of melanoma and targeted therapy
W Guo, H Wang, C Li |
Signal Transduction and Targeted Therapy | 2021 |
A Novel Ferroptosis-Associated Gene Signature to Predict Prognosis in Patients with Uveal Melanoma
H Luo, C Ma |
Diagnostics | 2021 |
Stem Cell Therapy for Burns: Story so Far
NA Kareem, A Aijaz, MG Jeschke |
Biologics : targets & therapy | 2021 |
Aetiology and Pathogenesis of Cutaneous Melanoma: Current Concepts and Advances
S Strashilov, A Yordanov |
International journal of molecular sciences | 2021 |
Converting melanoma-associated fibroblasts into a tumor-suppressive phenotype by increasing intracellular Notch1 pathway activity
H Shao, M Moller, L Cai, R Prokupets, C Yang, C Costa, K Yu, N Le, ZJ Liu, SV Pizzo |
PloS one | 2021 |
Increased Expression of VANGL1 is Predictive of Lymph Node Metastasis in Colorectal Cancer: Results from a 20-Gene Expression Signature
N Peyravian, S Nobili, Z Pezeshkian, M Olfatifar, A Moradi, K Baghaei, F Anaraki, K Nazari, HA Aghdaei, MR Zali, E Mini, EN Mojarad |
Journal of Personalized Medicine | 2021 |
Adipose mesenchymal stem cells combined with platelet-rich plasma accelerate diabetic wound healing by modulating the Notch pathway
N Ebrahim, AA Dessouky, O Mostafa, A Hassouna, MM Yousef, Y Seleem, EA Gebaly, MM Allam, AS Farid, BA Saffaf, D Sabry, A Nawar, AA Shoulah, AH Khalil, SF Abdalla, M El-Sherbiny, NM Elsherbiny, RF Salim |
Stem Cell Research & Therapy | 2021 |
Gender-Dependent Specificities in Cutaneous Melanoma Predisposition, Risk Factors, Somatic Mutations, Prognostic and Predictive Factors: A Systematic Review
O DEcclesiis, S Caini, C Martinoli, S Raimondi, C Gaiaschi, G Tosti, P Queirolo, C Veneri, C Saieva, S Gandini, S Chiocca |
International journal of environmental research and public health | 2021 |
Comprehensive molecular profiling of UV-induced metastatic melanoma in Nme1/Nme2-deficient mice reveals novel markers of survival in human patients
MK Leonard, GS Puts, N Pamidimukkala, G Adhikary, Y Xu, E Kwok, Y Jin, D Snyder, N Matsangos, M Novak, A Mahurkar, AC Shetty, RM Slominski, EC Fabo, FP Noonan, CP Day, M Rigi, AT Slominski, MG Webb, DW Craig, G Merlino, RL Eckert, JD Carpten, Z Manojlovic, DM Kaetzel |
Oncogene | 2021 |
Biology and Treatment Advances in Cutaneous Squamous Cell Carcinoma
AA Thai, AM Lim, BJ Solomon, D Rischin |
Cancers | 2021 |
Clinical Features and Prognostic Significance of NOTCH1 Mutations in Diffuse Large B-Cell Lymphoma
Li Z, Yu F, Ye W, Mao L, Huang J, Shao Y, Yan J, Yu W, Jin J, Wang J |
Frontiers in Oncology | 2021 |
NUMB as a Therapeutic Target for Melanoma
Hristova DM, Fukumoto T, Takemori C, Gao L, Hua X, Wang JX, Li L, Beqiri M, Watters A, Vultur A, Gimie Y, Rebecca V, Samarkina A, Jimbo H, Nishigori C, Zhang J, Cheng C, Wei Z, Somasundaram R, Fukunaga-Kalabis M, Herlyn M |
Journal of Investigative Dermatology | 2021 |