Lixin Wan, PhD
Researcher

Lixin Wan, PhD

Academic Rank: Assistant Member

Overview

The Wan lab is focused on the regulation and role of Anaphase-Promoting Complexes (APC) in directing the destruction of key proteins that control transit through the cell cycle, and in shaping proteomic networks in normal versus cancer cells. The lab is now investigating how APC complexes are rewired in cancer cells, and during the acquisition of resistance to targeted and conventional therapeutics. The long term goal of the lab is to define vulnerabilities in these circuits to develop novel anti-cancer therapies.

Discipline

    • Molecular Oncology
    • Cutaneous Oncology
    • Chemical Biology and Molecular Medicine Program

Education & Training

    • Chinese Academy of Sciences, PhD - Molecular Biology
    • Beth Israel Deaconess Medical Center Harvard Medical School, Fellow - Pathology
Publications

  • Takada M, Zhang W, Suzuki A, Kuroda T, Yu Z, Inuzuka H, Gao D, Wan L, Zhuang M, Hu L, Zhai B, Fry C, Bloom K, Li G, Karpen G, Wei W, Zhang Q. FBW7 Loss Promotes Chromosomal Instability and Tumorigenesis via Cyclin E1/CDK2-Mediated Phosphorylation of CENP-A. Cancer Res. 2017 Sep;77(18):4881-4893. Pubmedid: 28760857.
  • Huang LY, Wang X, Cui XF, Li H, Zhao J, Wu CC, Min L, Zhou Z, Wan L, Wang YP, Zhang C, Gao WQ, Sun Y, Han ZG. IRTKS is correlated with progression and survival time of patients with gastric cancer. Gut. 2017 Jun. Pubmedid: 28647685.
  • Wu F, Dai X, Gan W, Wan L, Li M, Mitsiades N, Wei W, Ding Q, Zhang J. Prostate cancer-associated mutation in SPOP impairs its ability to target Cdc20 for poly-ubiquitination and degradation. Cancer Lett. 2017 Jan;385:207-214. Pubmedid: 27780719. Pmcid: PMC5148662.
  • Lin S, Lu S, Mulaj M, Fang B, Keeley T, Wan L, Hao J, Muschol M, Sun J, Yang S. Monoubiquitination Inhibits the Actin Bundling Activity of Fascin. J Biol Chem. 2016 12;291(53):27323-27333. Pubmedid: 27879315. Pmcid: PMC5207158.
  • Cao J, Dai X, Wan L, Wang H, Zhang J, Goff PS, Sviderskaya EV, Xuan Z, Xu Z, Xu X, Hinds P, Flaherty KT, Faller DV, Goding CR, Wang Y, Wei W, Cui R. The E3 ligase APC/C(Cdh1) promotes ubiquitylation-mediated proteolysis of PAX3 to suppress melanocyte proliferation and melanoma growth. Sci Signal. 2015 Sep;8(392):ra87. Pubmedid: 26329581.
  • Wang L, Zhang J, Wan L, Zhou X, Wang Z, Wei W. Targeting Cdc20 as a novel cancer therapeutic strategy. Pharmacol Ther. 2015 Jul;151:141-151. Pubmedid: 25850036. Pmcid: PMC4457591.
  • Wan L, Tan M, Yang J, Inuzuka H, Dai X, Wu T, Liu J, Shaik S, Chen G, Deng J, Malumbres M, Letai A, Kirschner MW, Sun Y, Wei W. APC(Cdc20) suppresses apoptosis through targeting Bim for ubiquitination and destruction. Dev Cell. 2014 May;29(4):377-391. Pubmedid: 24871945. Pmcid: PMC4081014.
  • Liu J, Wan L, Liu P, Inuzuka H, Liu J, Wang Z, Wei W. SCF(β-TRCP)-mediated degradation of NEDD4 inhibits tumorigenesis through modulating the PTEN/Akt signaling pathway. Oncotarget. 2014 Feb;5(4):1026-1037. Pubmedid: 24657926. Pmcid: PMC4011580.
  • Liu P, Begley M, Michowski W, Inuzuka H, Ginzberg M, Gao D, Tsou P, Gan W, Papa A, Kim BM, Wan L, Singh A, Zhai B, Yuan M, Wang Z, Gygi SP, Lee TH, Lu KP, Toker A, Pandolfi PP, Asara JM, Kirschner MW, Sicinski P, Cantley L, Wei W. Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus. Nature. 2014 Apr;508(7497):541-545. Pubmedid: 24670654. Pmcid: PMC4076493.
  • Papa A, Wan L, Bonora M, Salmena L, Song MS, Hobbs RM, Lunardi A, Webster K, Ng C, Newton RH, Knoblauch N, Guarnerio J, Ito K, Turka LA, Beck AH, Pinton P, Bronson RT, Wei W, Pandolfi PP. Cancer-associated PTEN mutants act in a dominant-negative manner to suppress PTEN protein function. Cell. 2014 Apr;157(3):595-610. Pubmedid: 24766807. Pmcid: PMC4098792.
  • Zhang J, Wan L, Dai X, Sun Y, Wei W. Functional characterization of Anaphase Promoting Complex/Cyclosome (APC/C) E3 ubiquitin ligases in tumorigenesis. Biochim Biophys Acta. 2014 Apr;1845(2):277-293. Pubmedid: 24569229. Pmcid: PMC3995847.
  • Liu P, Gan W, Inuzuka H, Lazorchak AS, Gao D, Arojo O, Liu D, Wan L, Zhai B, Yu Y, Yuan M, Kim BM, Shaik S, Menon S, Gygi SP, Lee TH, Asara JM, Manning BD, Blenis J, Su B, Wei W. Sin1 phosphorylation impairs mTORC2 complex integrity and inhibits downstream Akt signalling to suppress tumorigenesis. Nat Cell Biol. 2013 Nov;15(11):1340-1350. Pubmedid: 24161930. Pmcid: PMC3827117.
  • Lau AW, Inuzuka H, Fukushima H, Wan L, Liu P, Gao D, Sun Y, Wei W. Regulation of APC(Cdh1) E3 ligase activity by the Fbw7/cyclin E signaling axis contributes to the tumor suppressor function of Fbw7. Cell Res. 2013 Jul;23(7):947-961. Pubmedid: 23670162. Pmcid: PMC3698637.
  • Zhong J, Shaik S, Wan L, Tron AE, Wang Z, Sun L, Inuzuka H, Wei W. SCF β-TRCP targets MTSS1 for ubiquitination-mediated destruction to regulate cancer cell proliferation and migration. Oncotarget. 2013 Dec;4(12):2339-2353. Pubmedid: 24318128. Pmcid: PMC3926831.
  • Cao J, Wan L, Hacker E, Dai X, Lenna S, Jimenez-Cervantes C, Wang Y, Leslie NR, Xu GX, Widlund HR, Ryu B, Alani RM, Dutton-Regester K, Goding CR, Hayward NK, Wei W, Cui R. MC1R is a potent regulator of PTEN after UV exposure in melanocytes. Mol Cell. 2013 Aug;51(4):409-422. Pubmedid: 23973372. Pmcid: PMC3792490.
  • Fukushima H, Ogura K, Wan L, Lu Y, Li V, Gao D, Liu P, Lau AW, Wu T, Kirschner MW, Inuzuka H, Wei W. SCF-mediated Cdh1 degradation defines a negative feedback system that coordinates cell-cycle progression. Cell Rep. 2013 Aug;4(4):803-816. Pubmedid: 23972993. Pmcid: PMC3839583.
  • Wang Z, Wan L, Zhong J, Inuzuka H, Liu P, Sarkar FH, Wei W. Cdc20: a potential novel therapeutic target for cancer treatment. Curr Pharm Des. 2013 Apr;19(18):3210-3214. Pubmedid: 23151139. Pmcid: PMC4014638.
  • Wang Z, Inuzuka H, Zhong J, Fukushima H, Wan L, Liu P, Wei W. DNA damage-induced activation of ATM promotes β-TRCP-mediated Mdm2 ubiquitination and destruction. Oncotarget. 2012 Sep;3(9):1026-1035. Pubmedid: 22976441. Pmcid: PMC3660052.
  • Fukushima H, Matsumoto A, Inuzuka H, Zhai B, Lau AW, Wan L, Gao D, Shaik S, Yuan M, Gygi SP, Jimi E, Asara JM, Nakayama K, Nakayama KI, Wei W. SCF(Fbw7) modulates the NFkB signaling pathway by targeting NFkB2 for ubiquitination and destruction. Cell Rep. 2012 May;1(5):434-443. Pubmedid: 22708077. Pmcid: PMC3375724.
  • Wang Z, Inuzuka H, Zhong J, Wan L, Fukushima H, Sarkar FH, Wei W. Tumor suppressor functions of FBW7 in cancer development and progression. FEBS Lett. 2012 May;586(10):1409-1418. Pubmedid: 22673505. Pmcid: PMC3372850.
  • Shaik S, Nucera C, Inuzuka H, Gao D, Garnaas M, Frechette G, Harris L, Wan L, Fukushima H, Husain A, Nose V, Fadda G, Sadow PM, Goessling W, North T, Lawler J, Wei W. SCF(β-TRCP) suppresses angiogenesis and thyroid cancer cell migration by promoting ubiquitination and destruction of VEGF receptor 2. J Exp Med. 2012 Jul;209(7):1289-1307. Pubmedid: 22711876. Pmcid: PMC3405505.
  • Inuzuka H, Gao D, Finley LW, Yang W, Wan L, Fukushima H, Chin YR, Zhai B, Shaik S, Lau AW, Wang Z, Gygi SP, Nakayama K, Teruya-Feldstein J, Toker A, Haigis MC, Pandolfi PP, Wei W. Acetylation-dependent regulation of Skp2 function. Cell. 2012 Jul;150(1):179-193. Pubmedid: 22770219. Pmcid: PMC3595190.
  • Wang Z, Gao D, Fukushima H, Inuzuka H, Liu P, Wan L, Sarkar FH, Wei W. Skp2: a novel potential therapeutic target for prostate cancer. Biochim Biophys Acta. 2012 Jan;1825(1):11-17. Pubmedid: 21963805. Pmcid: PMC3242930.
  • Wang Z, Fukushima H, Inuzuka H, Wan L, Liu P, Gao D, Sarkar FH, Wei W. Skp2 is a promising therapeutic target in breast cancer. Front Oncol. 2012 Jan;1(57). Pubmedid: 22279619. Pmcid: PMC3263529.
  • Gao D, Inuzuka H, Tan MK, Fukushima H, Locasale JW, Liu P, Wan L, Zhai B, Chin YR, Shaik S, Lyssiotis CA, Gygi SP, Toker A, Cantley LC, Asara JM, Harper JW, Wei W. mTOR drives its own activation via SCF(βTrCP)-dependent degradation of the mTOR inhibitor DEPTOR. Mol Cell. 2011 Oct;44(2):290-303. Pubmedid: 22017875. Pmcid: PMC3229299.
  • Wang Z, Fukushima H, Gao D, Inuzuka H, Wan L, Lau AW, Liu P, Wei W. The two faces of FBW7 in cancer drug resistance. Bioessays. 2011 Nov;33(11):851-859. Pubmedid: 22006825. Pmcid: PMC3364519.
  • Inuzuka H, Shaik S, Onoyama I, Gao D, Tseng A, Maser RS, Zhai B, Wan L, Gutierrez A, Lau AW, Xiao Y, Christie AL, Aster J, Settleman J, Gygi SP, Kung AL, Look T, Nakayama KI, DePinho RA, Wei W. SCF(FBW7) regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction. Nature. 2011 Mar;471(7336):104-109. Pubmedid: 21368833. Pmcid: PMC3076007.
  • Wang Z, Inuzuka H, Fukushima H, Wan L, Gao D, Shaik S, Sarkar FH, Wei W. Emerging roles of the FBW7 tumour suppressor in stem cell differentiation. EMBO Rep. 2011 Dec;13(1):36-43. Pubmedid: 22157894. Pmcid: PMC3246256.
  • Wan L, Zou W, Gao D, Inuzuka H, Fukushima H, Berg AH, Drapp R, Shaik S, Hu D, Lester C, Eguren M, Malumbres M, Glimcher LH, Wei W. Cdh1 regulates osteoblast function through an APC/C-independent modulation of Smurf1. Mol Cell. 2011 Dec;44(5):721-733. Pubmedid: 22152476. Pmcid: PMC3240853.
  • Gao D, Wan L, Wei W. Phosphorylation of Rictor at Thr1135 impairs the Rictor/Cullin-1 complex to ubiquitinate SGK1. Protein Cell. 2010 Oct;1(10):881-885. Pubmedid: 21204013. Pmcid: PMC3374330.
  • Gao D, Inuzuka H, Korenjak M, Tseng A, Wu T, Wan L, Kirschner M, Dyson N, Wei W. Cdh1 regulates cell cycle through modulating the claspin/Chk1 and the Rb/E2F1 pathways. Mol Biol Cell. 2009 Jul;20(14):3305-3316. Pubmedid: 19477924. Pmcid: PMC2710831.