Homeostatic and Tumourigenic Activity of SOX2+ Pituitary Stem Cells is Controlled by the LATS/YAP/TAZ Cascade

Overview

Journal Elife

Specialty Biology

Date 2019 Mar 27

PMID 30912742

Citations 19

Authors

Emily J Lodge

Alice Santambrogio

John P Russell

Paraskevi Xekouki

Thomas S Jacques

Randy L Johnson

Selvam Thavaraj

Stefan R Bornstein

Cynthia Lilian Andoniadou

Affiliations

Soon will be listed here.

Abstract

SOX2 positive pituitary stem cells (PSCs) are specified embryonically and persist throughout life, giving rise to all pituitary endocrine lineages. We have previously shown the activation of the STK/LATS/YAP/TAZ signalling cascade in the developing and postnatal mammalian pituitary. Here, we investigate the function of this pathway during pituitary development and in the regulation of the SOX2 cell compartment. Through loss- and gain-of-function genetic approaches, we reveal that restricting YAP/TAZ activation during development is essential for normal organ size and specification from SOX2+ PSCs. Postnatal deletion of LATS kinases and subsequent upregulation of YAP/TAZ leads to uncontrolled clonal expansion of the SOX2+ PSCs and disruption of their differentiation, causing the formation of non-secreting, aggressive pituitary tumours. In contrast, sustained expression of YAP alone results in expansion of SOX2+ PSCs capable of differentiation and devoid of tumourigenic potential. Our findings identify the LATS/YAP/TAZ signalling cascade as an essential component of PSC regulation in normal pituitary physiology and tumourigenesis.

Citing Articles

The circadian gene ARNTL2 promotes nasopharyngeal carcinoma invasiveness and metastasis through suppressing AMOTL2-LATS-YAP pathway.

Zou W, Lei Y, Ding C, Xiao H, Wang S, Liang S Cell Death Dis. 2024; 15(7):466.

PMID: 38956029 PMC: 11220028. DOI: 10.1038/s41419-024-06860-x.

Pathogenesis, clinical features, and treatment of plurihormonal pituitary adenoma.

Cai Y, Liu S, Zhao X, Ren L, Liu X, Gang X Front Neurosci. 2024; 17:1323883.

PMID: 38260014 PMC: 10800528. DOI: 10.3389/fnins.2023.1323883.

Pituitary stem cells: past, present and future perspectives.

Perez Millan M, Cheung L, Mercogliano F, Camilletti M, Chirino Felker G, Moro L Nat Rev Endocrinol. 2023; 20(2):77-92.

PMID: 38102391 PMC: 10964491. DOI: 10.1038/s41574-023-00922-4.

The Fuzzy planar cell polarity protein (FUZ), necessary for primary cilium formation, is essential for pituitary development.

Lodge E, Barrell W, Liu K, Andoniadou C J Anat. 2023; 244(2):358-367.

PMID: 37794731 PMC: 10780146. DOI: 10.1111/joa.13961.

Pituitary Tumorigenesis-Implications for Management.

Vamvoukaki R, Chrysoulaki M, Betsi G, Xekouki P Medicina (Kaunas). 2023; 59(4).

PMID: 37109772 PMC: 10145673. DOI: 10.3390/medicina59040812.

References

Cheung L, Rizzoti K, Lovell-Badge R, Le Tissier P . Pituitary phenotypes of mice lacking the notch signalling ligand delta-like 1 homologue. J Neuroendocrinol. 2013; 25(4):391-401. PMC: 3664429. DOI: 10.1111/jne.12010. View

Saeger W, Ludecke D, Buchfelder M, Fahlbusch R, Quabbe H, Petersenn S . Pathohistological classification of pituitary tumors: 10 years of experience with the German Pituitary Tumor Registry. Eur J Endocrinol. 2007; 156(2):203-16. DOI: 10.1530/eje.1.02326. View

Zhou D, Zhang Y, Wu H, Barry E, Yin Y, Lawrence E . Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance. Proc Natl Acad Sci U S A. 2011; 108(49):E1312-20. PMC: 3241824. DOI: 10.1073/pnas.1110428108. View

Levy A . Physiological implications of pituitary trophic activity. J Endocrinol. 2002; 174(2):147-55. DOI: 10.1677/joe.0.1740147. View

Lavado A, Park J, Pare J, Finkelstein D, Pan H, Xu B . The Hippo Pathway Prevents YAP/TAZ-Driven Hypertranscription and Controls Neural Progenitor Number. Dev Cell. 2018; 47(5):576-591.e8. PMC: 6296252. DOI: 10.1016/j.devcel.2018.09.021. View

Nantie L, Young R, Paltzer W, Zhang Y, Johnson R, Verheyden J . inactivation reveals Hippo function in alveolar type I cell differentiation during lung transition to air breathing. Development. 2018; 145(21). PMC: 6240317. DOI: 10.1242/dev.163105. View

Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T . Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012; 9(7):676-82. PMC: 3855844. DOI: 10.1038/nmeth.2019. View

Pulichino A, Vallette-Kasic S, Tsai J, Couture C, Gauthier Y, Drouin J . Tpit determines alternate fates during pituitary cell differentiation. Genes Dev. 2003; 17(6):738-47. PMC: 196016. DOI: 10.1101/gad.1065703. View

Muzumdar M, Tasic B, Miyamichi K, Li L, Luo L . A global double-fluorescent Cre reporter mouse. Genesis. 2007; 45(9):593-605. DOI: 10.1002/dvg.20335. View

10.

Lee J, Kavanagh J, Wildrick D, Wharton J, Blick M . Frequent loss of heterozygosity on chromosomes 6q, 11, and 17 in human ovarian carcinomas. Cancer Res. 1990; 50(9):2724-8. View

11.

Chen C, Yeh S, Chen D, Chen P, Jou Y . Molecular genetic evidence supporting a novel human hepatocellular carcinoma tumor suppressor locus at 13q12.11. Genes Chromosomes Cancer. 2005; 44(3):320-8. DOI: 10.1002/gcc.20247. View

12.

Lodge E, Russell J, Patist A, Francis-West P, Andoniadou C . Expression Analysis of the Hippo Cascade Indicates a Role in Pituitary Stem Cell Development. Front Physiol. 2016; 7:114. PMC: 4814506. DOI: 10.3389/fphys.2016.00114. View

13.

Moroishi T, Park H, Qin B, Chen Q, Meng Z, Plouffe S . A YAP/TAZ-induced feedback mechanism regulates Hippo pathway homeostasis. Genes Dev. 2015; 29(12):1271-84. PMC: 4495398. DOI: 10.1101/gad.262816.115. View

14.

Zhou Y, Huang T, Cheng A, Yu J, Kang W, To K . The TEAD Family and Its Oncogenic Role in Promoting Tumorigenesis. Int J Mol Sci. 2016; 17(1). PMC: 4730377. DOI: 10.3390/ijms17010138. View

15.

St John M, Tao W, Fei X, Fukumoto R, Carcangiu M, Brownstein D . Mice deficient of Lats1 develop soft-tissue sarcomas, ovarian tumours and pituitary dysfunction. Nat Genet. 1999; 21(2):182-6. DOI: 10.1038/5965. View

16.

Hu J, Du W, Shelton S, Oldham M, DiPersio C, Klein O . An FAK-YAP-mTOR Signaling Axis Regulates Stem Cell-Based Tissue Renewal in Mice. Cell Stem Cell. 2017; 21(1):91-106.e6. PMC: 5501749. DOI: 10.1016/j.stem.2017.03.023. View

17.

Zhang H, Liu C, Zha Z, Zhao B, Yao J, Zhao S . TEAD transcription factors mediate the function of TAZ in cell growth and epithelial-mesenchymal transition. J Biol Chem. 2009; 284(20):13355-13362. PMC: 2679435. DOI: 10.1074/jbc.M900843200. View

18.

Jansson L, Larsson J . Normal hematopoietic stem cell function in mice with enforced expression of the Hippo signaling effector YAP1. PLoS One. 2012; 7(2):e32013. PMC: 3283704. DOI: 10.1371/journal.pone.0032013. View

19.

Gaston-Massuet C, Andoniadou C, Signore M, Sajedi E, Bird S, Turner J . Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development. Dev Biol. 2008; 324(2):322-33. PMC: 3606136. DOI: 10.1016/j.ydbio.2008.08.008. View

20.

Pefani D, Latusek R, Pires I, Grawenda A, Yee K, Hamilton G . RASSF1A-LATS1 signalling stabilizes replication forks by restricting CDK2-mediated phosphorylation of BRCA2. Nat Cell Biol. 2014; 16(10):962-71, 1-8. PMC: 4861244. DOI: 10.1038/ncb3035. View