The role of STK11/LKB1 in cancer biology: implications for ovarian tumorigenesis and progression

被引:1
作者
Kang, Jian [1 ,2 ]
Gallucci, Stefano [1 ,2 ]
Pan, Junqi [1 ,2 ]
Oakhill, Jonathan S. [1 ,2 ]
Sanij, Elaine [1 ,2 ,3 ,4 ]
机构
[1] St Vincents Inst Med Res, Melbourne, Vic, Australia
[2] Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic, Australia
[3] Monash Univ, Dept Biochem & Mol Biol, Melbourne, Vic, Australia
[4] Peter MacCallum Canc Ctr, Div Canc Res, Melbourne, Vic, Australia
来源
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2024年 / 12卷
基金
澳大利亚国家健康与医学研究理事会;
关键词
LKB1; STK11; cancer biology; ovarian cancer; metabolism; immunotherapy; targeted therapy; cancer signaling; PEUTZ-JEGHERS-SYNDROME; PHASE-II; LKB1; KINASE; PROTEIN; CARCINOMA; PATHWAY; GENE; LKB1/STK11; GROWTH;
D O I
10.3389/fcell.2024.1449543
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
STK11 (serine-threonine kinase 11), also known as LKB1 (liver kinase B1) is a highly conserved master kinase that regulates cellular metabolism and polarity through a complex signaling network involving AMPK and 12 other AMPK-related kinases. Germline mutations in LKB1 have been causatively linked to Peutz-Jeghers Syndrome (PJS), an autosomal dominant hereditary disease with high cancer susceptibility. The identification of inactivating somatic mutations in LKB1 in different types of cancer further supports its tumor suppressive role. Deleterious mutations in LKB1 are frequently observed in patients with epithelial ovarian cancer. However, its inconsistent effects on tumorigenesis and cancer progression suggest that its functional impact is genetic context-dependent, requiring cooperation with other oncogenic lesions. In this review, we summarize the pleiotropic functions of LKB1 and how its altered activity in cancer cells is linked to oncogenic proliferation and growth, metastasis, metabolic reprogramming, genomic instability, and immune modulation. We also review the current mechanistic understandings of this master kinase as well as therapeutic implications with particular focus on the effects of LKB1 deficiency in ovarian cancer pathogenesis. Lastly, we discuss whether LKB1 deficiency can be exploited as an Achilles heel in ovarian cancer.
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页数:16
相关论文
共 127 条
  • [81] LKB1 Haploinsufficiency Cooperates With Kras to Promote Pancreatic Cancer Through Suppression of p21-Dependent Growth Arrest
    Morton, Jennifer P.
    Jamieson, Nigel B.
    Karim, Saadia A.
    Athineos, Dimitris
    Ridgway, Rachel A.
    Nixon, Colin
    Mckay, Colin J.
    Carter, Ross
    Brunton, Valerie G.
    Frame, Margaret C.
    Ashworth, Alan
    Oien, Karin A.
    Evans, T. R. Jeffry
    Sansom, Owen J.
    [J]. GASTROENTEROLOGY, 2010, 139 (02) : 586 - 597
  • [82] LKB1 drives stasis and C/EBP-mediated reprogramming to an alveolar type II fate in lung cancer
    Murray, Christopher W.
    Brady, Jennifer J.
    Han, Mingqi
    Cai, Hongchen
    Tsai, Min K.
    Pierce, Sarah E.
    Cheng, Ran
    Demeter, Janos
    Feldser, David M.
    Jackson, Peter K.
    Shackelford, David B.
    Winslow, Monte M.
    [J]. NATURE COMMUNICATIONS, 2022, 13 (01)
  • [83] An LKB1-SIK Axis Suppresses Lung Tumor Growth and Controls Differentiation
    Murray, Christopher W.
    Brady, Jennifer J.
    Tsai, Min K.
    Li, Chuan
    Winters, Ian
    Tang, Rui
    Andrejka, Laura
    Ma, Rosanna K.
    Kunder, Christian A.
    Chu, Pauline
    Winslow, Monte M.
    [J]. CANCER DISCOVERY, 2019, 9 (11) : 1590 - 1605
  • [84] Nakau M, 2002, CANCER RES, V62, P4549
  • [85] Nasri H, 2014, J RES MED SCI, V19, P658
  • [86] Pant S, 2023, J CLIN ONCOL, V41
  • [87] Intact LKB1 activity is required for survival of dormant ovarian cancer spheroids
    Peart, Teresa
    Valdes, Yudith Ramos
    Correa, Rohann J. M.
    Fazio, Elena
    Bertrand, Monique
    McGee, Jacob
    Prefontaine, Michel
    Sugimoto, Akira
    DiMattia, Gabriel E.
    Shepherd, Trevor G.
    [J]. ONCOTARGET, 2015, 6 (26) : 22424 - 22438
  • [88] STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway
    Pencik, Jan
    Philippe, Cecile
    Schlederer, Michaela
    Atas, Emine
    Pecoraro, Matteo
    Grund-Groeschke, Sandra
    Li, Wen
    Tracz, Amanda
    Heidegger, Isabel
    Lagger, Sabine
    Trachtova, Karolina
    Oberhuber, Monika
    Heitzer, Ellen
    Aksoy, Osman
    Neubauer, Heidi A.
    Wingelhofer, Bettina
    Orlova, Anna
    Witzeneder, Nadine
    Dillinger, Thomas
    Redl, Elisa
    Greiner, Georg
    D'Andrea, David
    Ostman, Johnny R.
    Tangermann, Simone
    Hermanova, Ivana
    Schaefer, Georg
    Sternberg, Felix
    Pohl, Elena E.
    Sternberg, Christina
    Varady, Adam
    Horvath, Jaqueline
    Stoiber, Dagmar
    Malcolm, Tim I.
    Turner, Suzanne D.
    Parkes, Eileen E.
    Hantusch, Brigitte
    Egger, Gerda
    Rose-John, Stefan
    Poli, Valeria
    Jain, Suneil
    Armstrong, Chris W. D.
    Hoermann, Gregor
    Goffin, Vincent
    Aberger, Fritz
    Moriggl, Richard
    Carracedo, Arkaitz
    McKinney, Cathal
    Kennedy, Richard D.
    Klocker, Helmut
    Speicher, Michael R.
    [J]. MOLECULAR CANCER, 2023, 22 (01)
  • [89] NUAK1 (ARK5) Is Associated with Poor Prognosis in Ovarian Cancer
    Phippen, Neil T.
    Bateman, Nicholas W.
    Wang, Guisong
    Conrads, Kelly A.
    Ao, Wei
    Teng, Pang-ning
    Litzi, Tracy A.
    Oliver, Julie
    Maxwell, G. Larry
    Hamilton, Chad A.
    Darcy, Kathleen M.
    Conrads, Thomas P.
    [J]. FRONTIERS IN ONCOLOGY, 2016, 6
  • [90] Phenotypic Consequences of SLC25A40-ABCB1 Fusions beyond Drug Resistance in High-Grade Serous Ovarian Cancer
    Pishas, Kathleen, I
    Cowley, Karla J.
    Pandey, Ahwan
    Hoang, Therese
    Beach, Jessica A.
    Luu, Jennii
    Vary, Robert
    Smith, Lorey K.
    Shembrey, Carolyn E.
    Rashoo, Nineveh
    White, Madelynne O.
    Simpson, Kaylene J.
    Bild, Andrea
    Griffiths, Jason, I
    Cheasley, Dane
    Campbell, Ian
    Bowtell, David D. L.
    Christie, Elizabeth L.
    [J]. CANCERS, 2021, 13 (22)