WNT/β-catenin signaling regulates mitochondrial activity to alter the oncogenic potential of melanoma in a PTEN-dependent manner

被引：61

作者：

Brown, K. ^{[1
,6
]}

Yang, P. ^{[2
]}

Salvador, D. ^{[3
]}

Kulikauskas, R. ^{[2
]}

Ruohola-Baker, H. ^{[4
]}

Robitaille, A. M. ^{[2
]}

Chien, A. J. ^{[2
,5
]}

Moon, R. T. ^{[2
]}

Sherwood, V. ^{[1
,3
]}

机构：

[1] Univ East Anglia, Sch Pharm, Norwich Res Pk, Norwich, Norfolk, England

[2] Inst Stem Cell & Regenerat Med, Howard Hughes Med Inst, Dept Pharmacol, Seattle, WA USA

[3] Univ Dundee, Ninewells Hosp & Med Sch, Div Canc Res, Jacqui Wood Canc Ctr, Dundee DD1 9SY, Angus, Scotland

[4] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[5] Univ Washington, Div Dermatol, Seattle, WA 98195 USA

[6] NCI, Thorac & GI Oncol Branch, NIH, Bethesda, MD 20892 USA

来源：

ONCOGENE | 2017年 / 36卷 / 22期

关键词：

BETA-CATENIN; BRAF MUTATIONS; CLINICOPATHOLOGICAL FEATURES; DISEASE PROGRESSION; SECRETED PROTEINS; EXPRESSION; CANCER; TUMORS; PARKIN; DEGRADATION;

D O I：

10.1038/onc.2016.450

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Aberrant regulation of WNT/beta-catenin signaling has a crucial role in the onset and progression of cancers, where the effects are not always predictable depending on tumor context. In melanoma, for example, models of the disease predict differing effects of the WNT/beta-catenin pathway on metastatic progression. Understanding the processes that underpin the highly context-dependent nature of WNT/beta-catenin signaling in tumors is essential to achieve maximal therapeutic benefit from WNT inhibitory compounds. In this study, we have found that expression of the tumor suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), alters the invasive potential of melanoma cells in response to WNT/beta-catenin signaling, correlating with differing metabolic profiles. This alters the bioenergetic potential and mitochondrial activity of melanoma cells, triggered through regulation of prosurvival autophagy. Thus, WNT/beta-catenin signaling is a regulator of catabolic processes in cancer cells, which varies depending on the metabolic requirements of tumors.

引用

页码：3119 / 3136

页数：18

共 103 条

[1] Genomic Classification of Cutaneous Melanoma [J].

Akbani, Rehan ;

Akdemir, Kadir C. ;

Aksoy, B. Arman ;

Albert, Monique ;

Ally, Adrian ;

Amin, Samirkumar B. ;

Arachchi, Harindra ;

Arora, Arshi ;

Auman, J. Todd ;

Ayala, Brenda ;

Baboud, Julien ;

Balasundaram, Miruna ;

Balu, Saianand ;

Barnabas, Nandita ;

Bartlett, John ;

Bartlett, Pam ;

Bastian, Boris C. ;

Baylin, Stephen B. ;

Behera, Madhusmita ;

Belyaev, Dmitry ;

Benz, Christopher ;

Bernard, Brady ;

Beroukhim, Rameen ;

Bir, Natalie ;

Black, Aaron D. ;

Bodenheimer, Tom ;

Boice, Lori ;

Boland, Genevieve M. ;

Bono, Riccardo ;

Bootwalla, Moiz S. ;

Bosenberg, Marcus ;

Bowen, Jay ;

Bowlby, Reanne ;

Bristow, Christopher A. ;

Brockway-Lunardi, Laura ;

Brooks, Denise ;

Brzezinski, Jakub ;

Bshara, Wiam ;

Buda, Elizabeth ;

Burns, William R. ;

Butterfield, Yaron S. N. ;

Button, Michael ;

Calderone, Tiffany ;

Cappellini, Giancarlo Antonini ;

Carter, Candace ;

Carter, Scott L. ;

Cherney, Lynn ;

Cherniack, Andrew D. ;

Chevalier, Aaron ;

Chin, Lynda .

CELL, 2015, 161 (07) :1681-1696

[2] WNT signalling pathways as therapeutic targets in cancer [J].

Anastas, Jamie N. ;

Moon, Randall T. .

NATURE REVIEWS CANCER, 2013, 13 (01) :11-26

[3] The tumor suppressor PTEN positively regulates macroautophagy by inhibiting the phosphatidylinositol 3-kinase/protein kinase B pathway [J].

Arico, S ;

Petiot, A ;

Bauvy, C ;

Dubbelhuis, PF ;

Meijer, AJ ;

Codogno, P ;

Ogier-Denis, E .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (38) :35243-35246

[4] In melanoma, beta-catenin is a suppressor of invasion [J].

Arozarena, I. ;

Bischof, H. ;

Gilby, D. ;

Belloni, B. ;

Dummer, R. ;

Wellbrock, C. .

ONCOGENE, 2011, 30 (45) :4531-4543

[5] Regulation of GLUT1 gene transcription by the serine threonine kinase Akt1 [J].

Barthel, A ;

Okino, ST ;

Liao, JF ;

Nakatani, K ;

Li, JP ;

Whitlock, JP ;

Roth, RA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (29) :20281-20286

[6] Classifying melanocytic tumors based on DNA copy number changes [J].

Bastian, BC ;

Olshen, AB ;

LeBoit, PE ;

Pinkel, D .

AMERICAN JOURNAL OF PATHOLOGY, 2003, 163 (05) :1765-1770

[7] MONITORING AUTOPHAGIC DEGRADATION OF P62/SQSTM1 [J].

Bjorkoy, Geir ;

Lamark, Trond ;

Pankiv, Serhiy ;

Overvatn, Aud ;

Brech, Andreas ;

Johansen, Terje .

METHODS IN ENZYMOLOGY: AUTOPHAGY IN MAMMALIAN SYSTEMS, VOL 452, PT B, 2009, 452 :181-197

[8] Assessing mitochondrial dysfunction in cells [J].

Brand, Martin D. ;

Nicholls, David G. .

BIOCHEMICAL JOURNAL, 2011, 435 :297-312

[9] Balancing cell adhesion and Wnt signaling, the key role of β-catenin [J].

Brembeck, FH ;

Rosário, M ;

Birchmeier, W .

CURRENT OPINION IN GENETICS & DEVELOPMENT, 2006, 16 (01) :51-59

[10] Mitf regulation of Dia1 controls melanoma proliferation and invasiveness [J].

Carreira, Suzanne ;

Goodall, Jane ;

Denat, Laurence ;

Rodriguez, Mercedes ;

Nuciforo, Paolo ;

Hoek, Keith S. ;

Testori, Alessandro ;

Larue, Lionel ;

Goding, Colin R. .

GENES & DEVELOPMENT, 2006, 20 (24) :3426-3439

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