Epithelial-mesenchymal transition inhibition by metformin reduces melanoma lung metastasis in a murine model

被引：9

作者：

Veloso, Emerson Soares ^{[1
]}

de Carvalho, Barbara Andrade ^{[1
]}

de Souza Silva, Felipe Henrique ^{[1
]}

Ribeiro, Thais Salviana ^{[1
]}

Lima, Bruna Mendes ^{[1
]}

Almeida, Camila Pereira ^{[1
]}

Soares Romao da Silva, Vitor Henrique ^{[1
]}

Rocha, Sara Aparecida ^{[1
]}

de Araujo Campos, Marina Rios ^{[1
]}

Del Puerto, Helen Lima ^{[1
]}

Ferreira, Enio ^{[1
]}

机构：

[1] Univ Fed Minas Gerais, Inst Biol Sci, Dept Gen Pathol, BR-31270901 Belo Horizonte, MG, Brazil

来源：

SCIENTIFIC REPORTS | 2022年 / 12卷 / 01期

关键词：

E-CADHERIN; CANCER; EMT; EXPRESSION; MELANOGENESIS; PROGRESSION; MIGRATION; SWITCH;

D O I：

10.1038/s41598-022-22235-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Melanoma is an aggressive cancer with fast metastatic spread and reduced survival time. One common event during the neoplastic progression is the epithelial-mesenchymal transition (EMT), which enhances invasiveness, cell migration, and metastasis. In this study, we investigated the effects of metformin at EMT in melanoma cell lines B16-F10 and A-375, in vitro, and the impact of EMT downregulation on melanoma progression in vivo. The metformin cells treatment reduces the migration potential in vitro and reduced the development of pulmonary metastases and the expressions of N-cadherin, vimentin, ZEB1, and ZEB2 at the metastases site, in vivo. These results indicate that metformin can promote EMT downregulation impairing the metastatic potential of melanoma cells.

引用

页数：13

共 43 条

[1] Relative expression of KLK5 to LEKTI is associated with aggressiveness of oral squamous cell carcinoma [J].

Alves, Marcia Gaiao ;

Kodama, Marcio Hideki ;

Marcelino da Silva, Elaine Zayas ;

Martinelli Gomes, Bruno Belmonte ;

Alves da Silva, Rodrigo Alberto ;

Vieira, Gabriel Viliod ;

Alves, Vani Maria ;

da Fonseca, Carol Kobori ;

Santana, Ana Carolina ;

Cecilio, Nerry Tatiana ;

Alexandre Costa, Mara Silvia ;

Jamur, Maria Celia ;

Oliver, Constance ;

Cunha, Thiago Mattar ;

Bugge, Thomas H. ;

Braz-Silva, Paulo Henrique ;

Colli, Leandro M. ;

Sales, Katiuchia Uzzun .

TRANSLATIONAL ONCOLOGY, 2021, 14 (01)

[2] EMT: 2016 [J].

Angela Nieto, M. ;

Huang, Ruby Yun-Ju ;

Jackson, Rebecca A. ;

Thiery, Jean Paul .

CELL, 2016, 166 (01) :21-45

[3] MicroRNAs and Their Influence on the ZEB Family: Mechanistic Aspects and Therapeutic Applications in Cancer Therapy [J].

Ashrafizadeh, Milad ;

Ang, Hui Li ;

Moghadam, Ebrahim Rahmani ;

Mohammadi, Shima ;

Zarrin, Vahideh ;

Hushmandi, Kiavash ;

Samarghandian, Saeed ;

Zarrabi, Ali ;

Najafi, Masoud ;

Mohammadinejad, Reza ;

Kumar, Alan Prem .

BIOMOLECULES, 2020, 10 (07) :1-45

[4] Increased cancer-related mortality for patients with type 2 diabetes who use sulforrylureas or insulin [J].

Bowker, SL ;

Majumdar, SR ;

Veugelers, P ;

Johnson, JA .

DIABETES CARE, 2006, 29 (02) :254-258

[5] EMT in cancer [J].

Brabletz, Thomas ;

Kalluri, Raghu ;

Angela Nieto, M. ;

Weinberg, Robert A. .

NATURE REVIEWS CANCER, 2018, 18 (02) :128-+

[6] Intrinsic Balance between ZEB Family Members Is Important for Melanocyte Homeostasis and Melanoma Progression [J].

Bruneel, Kenneth ;

Verstappe, Jeroen ;

Vandamme, Niels ;

Berx, Geert .

CANCERS, 2020, 12 (08) :1-25

[7] A Switch in the Expression of Embryonic EMT-Inducers Drives the Development of Malignant Melanoma [J].

Caramel, Julie ;

Papadogeorgakis, Eftychios ;

Hill, Louise ;

Browne, Gareth J. ;

Richard, Geoffrey ;

Wierinckx, Anne ;

Saldanha, Gerald ;

Osborne, Joy ;

Hutchinson, Peter ;

Tse, Gina ;

Lachuer, Joel ;

Puisieux, Alain ;

Pringle, J. Howard ;

Ansieau, Stephane ;

Tulchinsky, Eugene .

CANCER CELL, 2013, 24 (04) :466-480

[8] Is it time to test biguanide metformin in the treatment of melanoma? [J].

Cerezo, Michael ;

Tomic, Tijana ;

Ballotti, Robert ;

Rocchi, Stephane .

PIGMENT CELL & MELANOMA RESEARCH, 2015, 28 (01) :8-20

[9] Metformin Blocks Melanoma Invasion and Metastasis Development in AMPK/p53-Dependent Manner [J].

Cerezo, Michael ;

Tichet, Melanie ;

Abbe, Patricia ;

Ohanna, Mickael ;

Lehraiki, Abdelali ;

Rouaud, Florian ;

Allegra, Maryline ;

Giacchero, Damien ;

Bahadoran, Philippe ;

Bertolotto, Corine ;

Tartare-Deckert, Sophie ;

Ballotti, Robert ;

Rocchi, Stephane .

MOLECULAR CANCER THERAPEUTICS, 2013, 12 (08) :1605-1615

[10] Repurposing metformin for cancer treatment: current clinical studies [J].

Chae, Young Kwang ;

Arya, Ayush ;

Malecek, Mary-Kate ;

Shin, Daniel Sanghoon ;

Carneiro, Benedito ;

Chandra, Sunandana ;

Kaplan, Jason ;

Kalyan, Aparna ;

Altman, Jessica K. ;

Platanias, Leonidas ;

Giles, Francis .

ONCOTARGET, 2016, 7 (26) :40767-40780

← 1 2 3 4 5 →