Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Cellular and Molecular Biology

Nuclear receptor TLX functions to promote cancer stemness and EMT in prostate cancer via its direct transactivation of CD44 and stem cell-regulatory transcription factors

British Journal of Cancer (2024)Cite this article

Subjects

Abstract

Background

Prostate cancer stem cells (PCSCs) play crucial roles in therapy-resistance and metastasis in castration-resistant prostate cancer (CRPC). Certain functional link between cancer stemness and epithelial-mesenchymal transition (EMT) is involved in CRPC. However, up-stream regulators controlling these two processes in PCSCs are still poorly understood. Recently, we have shown that orphan nuclear receptor TLX can promote tumour initiation and progression in CRPC by repressing androgen receptor and oncogene-induced senescence.

Methods

PCSCs were isolated from various prostate cancer cell lines and clinical tumour tissues using multiple methods for various in vitro and in vivo oncogenic growth analyses. Direct targets of TLX involved in stemness and EMT regulation were determined by specific reporter gene assays and ligand-driven modulation of TLX activity.

Results

PCSCs isolated from various sources exhibited increased expression of TLX. Functional and molecular characterisation showed that TLX could function to promote cancer stemness and EMT in prostate cancer cells via its direct transactivation of CD44, SOX2, POU5F1 and NANOG, which share certain functional crosstalk in these two cellular processes.

Conclusions

TLX could act as a key up-stream regulator in transcriptional control of stemness and EMT in PCSCs, which contribute to their tumorigenicity, castration-resistance and metastasis potentials in advanced prostate cancer.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Isolated PCSCs display increased TLX expression.
Fig. 2: TLX promotes clonogenicity of prostate cancer cells.
Fig. 3: TLX promotes in vitro migration and invasion capacities and in vivo metastasis potential of prostate cancer cells.
Fig. 4: Effects of TLX overexpression and its knockout on expressions of CSCs- and EMT-associated markers in prostate cancer cells.
Fig. 5: Direct transactivation of CD44 gene by TLX.
Fig. 6: SOX2, POU5F1 and NANOG as direct targets of TLX.

Similar content being viewed by others

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Aramini B, Masciale V, Grisendi G, Bertolini F, Maur M, Guaitoli G, et al. Dissecting tumor growth: the role of cancer stem cells in drug resistance and recurrence. Cancers (Basel). 2022;14:976.

    Article  CAS  PubMed  Google Scholar 

  2. Gao W, Wu D, Wang Y, Wang Z, Zou C, Dai Y, et al. Development of a novel and economical agar-based non-adherent three-dimensional culture method for enrichment of cancer stem-like cells. Stem Cell Res Ther. 2018;9:243.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wang Z, Wu D, Ng CF, Teoh JY, Yu S, Wang Y, et al. Nuclear receptor profiling in prostatospheroids and castration-resistant prostate cancer. Endocr Relat Cancer. 2018;25:35–50.

    Article  PubMed  Google Scholar 

  4. Tang DG. Understanding and targeting prostate cancer cell heterogeneity and plasticity. Semin Cancer Biol. 2022;82:68–93.

    Article  CAS  PubMed  Google Scholar 

  5. Wolf I, Gratzke C, Wolf P. Prostate cancer stem cells: clinical aspects and targeted therapies. Front Oncol. 2022;12:935715.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chaves LP, Melo CM, Saggioro FP, Reis RBD, Squire JA. Epithelial-mesenchymal transition signaling and prostate cancer stem cells: emerging biomarkers and opportunities for precision therapeutics. Genes (Basel). 2021;12:1900.

    Article  CAS  PubMed  Google Scholar 

  7. Brabletz S, Schuhwerk H, Brabletz T, Stemmler MP. Dynamic EMT: a multi-tool for tumor progression. EMBO J. 2021;40:e108647.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zheng X, Dai F, Feng L, Zou H, Feng L, Xu M. Communication between epithelial-mesenchymal plasticity and cancer stem cells: new insights into cancer progression. Front Oncol. 2021;11:617597.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yu RT, McKeown M, Evans RM, Umesono K. Relationship between Drosophila gap gene tailless and a vertebrate nuclear receptor Tlx. Nature. 1994;370:375–9.

    Article  CAS  PubMed  Google Scholar 

  10. Jackson A, Panayiotidis P, Foroni L. The human homologue of the Drosophila tailless gene (TLX): characterization and mapping to a region of common deletion in human lymphoid leukemia on chromosome 6q21. Genomics. 1998;50:34–43.

    Article  CAS  PubMed  Google Scholar 

  11. Monaghan AP, Grau E, Bock D, Schutz G. The mouse homolog of the orphan nuclear receptor tailless is expressed in the developing forebrain. Development. 1995;121:839–53.

    Article  CAS  PubMed  Google Scholar 

  12. Sun G, Cui Q, Shi Y. Nuclear receptor TLX in development and diseases. Curr Top Dev Biol. 2017;125:257–73.

    Article  CAS  PubMed  Google Scholar 

  13. Nelson AT, Wang Y, Nelson ER. TLX, an orphan nuclear receptor with emerging roles in physiology and disease. Endocrinology. 2021;162:1–13.

    Article  CAS  Google Scholar 

  14. Wu D, Cheung A, Wang Y, Yu S, Chan FL. The emerging roles of orphan nuclear receptors in prostate cancer. Biochim Biophys Acta. 2016;1866:23–36.

    CAS  PubMed  Google Scholar 

  15. Liu HK, Wang Y, Belz T, Bock D, Takacs A, Radlwimmer B, et al. The nuclear receptor tailless induces long-term neural stem cell expansion and brain tumor initiation. Genes Dev. 2010;24:683–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Zou Y, Niu W, Qin S, Downes M, Burns DK, Zhang CL. The nuclear receptor TLX is required for gliomagenesis within the adult neurogenic niche. Mol Cell Biol. 2012;32:4811–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chavali PL, Saini RK, Zhai Q, Vizlin-Hodzic D, Venkatabalasubramanian S, Hayashi A, et al. TLX activates MMP-2, promotes self-renewal of tumor spheres in neuroblastoma and correlates with poor patient survival. Cell Death Dis. 2014;5:e1502.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Lin ML, Patel H, Remenyi J, Banerji CR, Lai CF, Periyasamy M, et al. Expression profiling of nuclear receptors in breast cancer identifies TLX as a mediator of growth and invasion in triple-negative breast cancer. Oncotarget. 2015;6:21685–703.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Nelczyk AT, Ma L, Gupta AD, Gamage HEV, McHenry MT, Henn MA, et al. The nuclear receptor TLX (NR2E1) inhibits growth and progression of triple- negative breast cancer. Biochim Biophys Acta Mol Basis Dis. 2022;1868:166515.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Wu D, Yu S, Jia L, Zou C, Xu Z, Xiao L, et al. Orphan nuclear receptor TLX functions as a potent suppressor of oncogene-induced senescence in prostate cancer via its transcriptional co-regulation of the CDKN1A (p21(WAF1) (/) (CIP1)) and SIRT1 genes. J Pathol. 2015;236:103–15.

    Article  CAS  PubMed  Google Scholar 

  21. Jia L, Wu D, Wang Y, You W, Wang Z, Xiao L, et al. Orphan nuclear receptor TLX contributes to androgen insensitivity in castration-resistant prostate cancer via its repression of androgen receptor transcription. Oncogene. 2018;37:3340–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Zhou J, Pei X, Yang Y, Wang Z, Gao W, Ye R, et al. Orphan nuclear receptor TLX promotes immunosuppression via its transcriptional activation of PD-L1 in glioma. J Immunother Cancer. 2021;9:e001937.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Cheung CP, Yu S, Wong KB, Chan LW, Lai FM, Wang X, et al. Expression and functional study of estrogen receptor-related receptors in human prostatic cells and tissues. J Clin Endocrinol Metab. 2005;90:1830–44.

    Article  CAS  PubMed  Google Scholar 

  24. Gao W, Wang Y, Yu S, Wang Z, Ma T, Chan AM, et al. Endothelial nitric oxide synthase (eNOS)-NO signaling axis functions to promote the growth of prostate cancer stem-like cells. Stem Cell Res Ther. 2022;13:188.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Tang B, Raviv A, Esposito D, Flanders KC, Daniel C, Nghiem BT, et al. A flexible reporter system for direct observation and isolation of cancer stem cells. Stem Cell Rep. 2015;4:155–69.

    Article  Google Scholar 

  26. Yu S, Wang MW, Yao X, Chan FL. Establishment of a novel immortalized human prostatic epithelial cell line stably expressing androgen receptor and its application for the functional screening of androgen receptor modulators. Biochem Biophys Res Commun. 2009;382:756–61.

    Article  CAS  PubMed  Google Scholar 

  27. Yu S, Xu Z, Zou C, Wu D, Wang Y, Yao X, et al. Ion channel TRPM8 promotes hypoxic growth of prostate cancer cells via an O2 -independent and RACK1-mediated mechanism of HIF-1alpha stabilization. J Pathol. 2014;234:514–25.

    Article  CAS  PubMed  Google Scholar 

  28. Yu S, Jia L, Zhang Y, Wu D, Xu Z, Ng CF, et al. Increased expression of activated endothelial nitric oxide synthase contributes to antiandrogen resistance in prostate cancer cells by suppressing androgen receptor transactivation. Cancer Lett. 2013;328:83–94.

    Article  CAS  PubMed  Google Scholar 

  29. Yu S, Wong YC, Wang XH, Ling MT, Ng CF, Chen S, et al. Orphan nuclear receptor estrogen-related receptor-beta suppresses in vitro and in vivo growth of prostate cancer cells via p21(WAF1/CIP1) induction and as a potential therapeutic target in prostate cancer. Oncogene. 2008;27:3313–28.

    Article  CAS  PubMed  Google Scholar 

  30. Griffett K, Bedia-Diaz G, Hegazy L, de Vera IMS, Wanninayake US, Billon C, et al. The orphan nuclear receptor TLX is a receptor for synthetic and natural retinoids. Cell Chem Biol. 2020;27:1272–84.e4.

    Article  CAS  PubMed  Google Scholar 

  31. Benod C, Villagomez R, Filgueira CS, Hwang PK, Leonard PG, Poncet-Montange G, et al. The human orphan nuclear receptor tailless (TLX, NR2E1) is druggable. PLoS One. 2014;9:e99440.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Zou C, Yu S, Xu Z, Wu D, Ng CF, Yao X, et al. ERRalpha augments HIF-1 signalling by directly interacting with HIF-1alpha in normoxic and hypoxic prostate cancer cells. J Pathol. 2014;233:61–73.

    Article  CAS  PubMed  Google Scholar 

  33. Yu S, Wang X, Ng CF, Chen S, Chan FL. ERRgamma suppresses cell proliferation and tumor growth of androgen-sensitive and androgen-insensitive prostate cancer cells and its implication as a therapeutic target for prostate cancer. Cancer Res. 2007;67:4904–14.

    Article  CAS  PubMed  Google Scholar 

  34. Chu JH, Yu S, Hayward SW, Chan FL. Development of a three-dimensional culture model of prostatic epithelial cells and its use for the study of epithelial-mesenchymal transition and inhibition of PI3K pathway in prostate cancer. Prostate. 2009;69:428–42.

    Article  CAS  PubMed  Google Scholar 

  35. Rybak AP, He L, Kapoor A, Cutz JC, Tang D. Characterization of sphere-propagating cells with stem-like properties from DU145 prostate cancer cells. Biochim Biophys Acta. 2011;1813:683–94.

    Article  CAS  PubMed  Google Scholar 

  36. Liu X, Qiao Y, Ting X, Si W. Isocitrate dehydrogenase 3A, a rate-limiting enzyme of the TCA cycle, promotes hepatocellular carcinoma migration and invasion through regulation of MTA1, a core component of the NuRD complex. Am J Cancer Res. 2020;10:3212–29.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Morath I, Hartmann TN, Orian-Rousseau V. CD44: More than a mere stem cell marker. Int J Biochem Cell Biol. 2016;81:166–73.

    Article  CAS  PubMed  Google Scholar 

  38. Shi Y, Chichung Lie D, Taupin P, Nakashima K, Ray J, Yu RT, et al. Expression and function of orphan nuclear receptor TLX in adult neural stem cells. Nature. 2004;427:78–83.

    Article  CAS  PubMed  Google Scholar 

  39. Zhang CL, Zou Y, He W, Gage FH, Evans RM. A role for adult TLX-positive neural stem cells in learning and behaviour. Nature. 2008;451:1004–7.

    Article  CAS  PubMed  Google Scholar 

  40. Elmi M, Matsumoto Y, Zeng ZJ, Lakshminarasimhan P, Yang W, Uemura A, et al. TLX activates MASH1 for induction of neuronal lineage commitment of adult hippocampal neuroprogenitors. Mol Cell Neurosci. 2010;45:121–31.

    Article  CAS  PubMed  Google Scholar 

  41. Li W, Sun G, Yang S, Qu Q, Nakashima K, Shi Y. Nuclear receptor TLX regulates cell cycle progression in neural stem cells of the developing brain. Mol Endocrinol. 2008;22:56–64.

    Article  CAS  PubMed  Google Scholar 

  42. Sun G, Yu RT, Evans RM, Shi Y. Orphan nuclear receptor TLX recruits histone deacetylases to repress transcription and regulate neural stem cell proliferation. Proc Natl Acad Sci USA. 2007;104:15282–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Luque-Molina I, Shi Y, Abdullah Y, Monaco S, Holzl-Wenig G, Mandl C, et al. The orphan nuclear receptor TLX represses Hes1 expression, thereby affecting NOTCH signaling and lineage progression in the adult SEZ. Stem Cell Rep. 2019;13:132–46.

    Article  CAS  Google Scholar 

  44. Ou CY, Poon VY, Maeder CI, Watanabe S, Lehrman EK, Fu AK, et al. Two cyclin-dependent kinase pathways are essential for polarized trafficking of presynaptic components. Cell. 2010;141:846–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Cui Q, Yang S, Ye P, Tian E, Sun G, Zhou J, et al. Downregulation of TLX induces TET3 expression and inhibits glioblastoma stem cell self-renewal and tumorigenesis. Nat Commun. 2016;7:10637.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Chanmee T, Ontong P, Kimata K, Itano N. Key roles of hyaluronan and its CD44 receptor in the stemness and survival of cancer stem cells. Front Oncol. 2015;5:180.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ. Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res. 2005;65:10946–51.

    Article  CAS  PubMed  Google Scholar 

  48. Aaltomaa S, Lipponen P, Ala-Opas M, Kosma VM. Expression and prognostic value of CD44 standard and variant v3 and v6 isoforms in prostate cancer. Eur Urol. 2001;39:138–44.

    Article  CAS  PubMed  Google Scholar 

  49. De Marzo AM, Bradshaw C, Sauvageot J, Epstein JI, Miller GJ. CD44 and CD44v6 downregulation in clinical prostatic carcinoma: relation to Gleason grade and cytoarchitecture. Prostate. 1998;34:162–8.

    Article  PubMed  Google Scholar 

  50. Gao AC, Lou W, Dong JT, Isaacs JT. CD44 is a metastasis suppressor gene for prostatic cancer located on human chromosome 11p13. Cancer Res. 1997;57:846–9.

    CAS  PubMed  Google Scholar 

  51. Fontanella RA, Sideri S, Di Stefano C, Catizone A, Di Agostino S, Angelini DF, et al. CD44v8-10 is a marker for malignant traits and a potential driver of bone metastasis in a subpopulation of prostate cancer cells. Cancer Biol Med. 2021;18:788–807.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Hurt EM, Kawasaki BT, Klarmann GJ, Thomas SB, Farrar WL. CD44+ CD24(-) prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis. Br J Cancer. 2008;98:756–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Patrawala L, Calhoun T, Schneider-Broussard R, Li H, Bhatia B, Tang S, et al. Highly purified CD44+ prostate cancer cells from xenograft human tumors are enriched in tumorigenic and metastatic progenitor cells. Oncogene. 2006;25:1696–708.

    Article  CAS  PubMed  Google Scholar 

  54. Hao J, Chen H, Madigan MC, Cozzi PJ, Beretov J, Xiao W, et al. Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression. Br J Cancer. 2010;103:1008–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Hernandez JR, Kim JJ, Verdone JE, Liu X, Torga G, Pienta KJ, et al. Alternative CD44 splicing identifies epithelial prostate cancer cells from the mesenchymal counterparts. Med Oncol. 2015;32:159.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Ni J, Cozzi PJ, Hao JL, Beretov J, Chang L, Duan W, et al. CD44 variant 6 is associated with prostate cancer metastasis and chemo-/radioresistance. Prostate. 2014;74:602–17.

    Article  CAS  PubMed  Google Scholar 

  57. Kwon OJ, Zhang L, Jia D, Xin L. Sox2 is necessary for androgen ablation-induced neuroendocrine differentiation from Pten null Sca-1(+) prostate luminal cells. Oncogene. 2021;40:203–14.

    Article  CAS  PubMed  Google Scholar 

  58. Matsika A, Srinivasan B, Day C, Mader SA, Kiernan DM, Broomfield A, et al. Cancer stem cell markers in prostate cancer: an immunohistochemical study of ALDH1, SOX2 and EZH2. Pathology. 2015;47:622–8.

    Article  CAS  PubMed  Google Scholar 

  59. Russo MV, Esposito S, Tupone MG, Manzoli L, Airoldi I, Pompa P, et al. SOX2 boosts major tumor progression genes in prostate cancer and is a functional biomarker of lymph node metastasis. Oncotarget. 2016;7:12372–85.

    Article  PubMed  Google Scholar 

  60. Kregel S, Kiriluk KJ, Rosen AM, Cai Y, Reyes EE, Otto KB, et al. Sox2 is an androgen receptor-repressed gene that promotes castration-resistant prostate cancer. PLoS One. 2013;8:e53701.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Rybak AP, Tang D. SOX2 plays a critical role in EGFR-mediated self-renewal of human prostate cancer stem-like cells. Cell Signal. 2013;25:2734–42.

    Article  CAS  PubMed  Google Scholar 

  62. de Wet L, Williams A, Gillard M, Kregel S, Lamperis S, Gutgesell LC, et al. SOX2 mediates metabolic reprogramming of prostate cancer cells. Oncogene. 2022;41:1190–202.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Sotomayor P, Godoy A, Smith GJ, Huss WJ. Oct4A is expressed by a subpopulation of prostate neuroendocrine cells. Prostate. 2009;69:401–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Jeter CR, Liu B, Liu X, Chen X, Liu C, Calhoun-Davis T, et al. NANOG promotes cancer stem cell characteristics and prostate cancer resistance to androgen deprivation. Oncogene. 2011;30:3833–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Jeter CR, Liu B, Lu Y, Chao HP, Zhang D, Liu X, et al. NANOG reprograms prostate cancer cells to castration resistance via dynamically repressing and engaging the AR/FOXA1 signaling axis. Cell Discov. 2016;2:16041.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Chavali PL, Saini RK, Matsumoto Y, Agren H, Funa K. Nuclear orphan receptor TLX induces Oct-3/4 for the survival and maintenance of adult hippocampal progenitors upon hypoxia. J Biol Chem. 2011;286:9393–404.

    Article  CAS  PubMed  Google Scholar 

  67. Islam MM, Smith DK, Niu W, Fang S, Iqbal N, Sun G, et al. Enhancer analysis unveils genetic interactions between TLX and SOX2 in neural stem cells and in vivo reprogramming. Stem Cell Rep. 2015;5:805–15.

    Article  CAS  Google Scholar 

  68. Kandel P, Semerci F, Mishra R, Choi W, Bajic A, Baluya D, et al. Oleic acid is an endogenous ligand of TLX/NR2E1 that triggers hippocampal neurogenesis. Proc Natl Acad Sci USA. 2022;119:e2023784119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Liotti A, Cosimato V, Mirra P, Cali G, Conza D, Secondo A, et al. Oleic acid promotes prostate cancer malignant phenotype via the G protein-coupled receptor FFA1/GPR40. J Cell Physiol. 2018;233:7367–78.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank Dr. Wakefield LM (NIH) for the SORE6-GFP lentiviral plasmid.

Funding

This work was supported by grants from the General Research Fund (project no. 14110918) from the Research Grants Council of Hong Kong (to Chan FL), National Natural Science Foundation of China (Nos. 81872283 and 82273341), Guangdong Basic and Applied Basic Research Foundation (2024A1515011645), Science and Technology Project of Shenzhen (GJHZ20220913144209018) and Research Foundation of Shenzhen Hospital of Southern Medical University (No. 22H3ATF02) (to Wu D).

Author information

Author notes

  1. These authors contributed equally: Sin Ting Chow, Jiaqi Fan.

Authors and Affiliations

  1. School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong, China

    Sin Ting Chow, Jiaqi Fan, Xingxing Zhang, Yuliang Wang, Youjia Li & Franky Leung Chan

  2. Department of Surgery, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Hong Kong, China

    Chi-Fai Ng & Dinglan Wu

  3. Department of Pathology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guandong, China

    Xiaojuan Pei

  4. Department of Urology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong Province, China

    Qingyou Zheng

  5. Department of Urology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, China

    Fei Wang

  6. Department of Urology and The Clinical Innovation & Research Center (CIRC), Shenzhen Hospital, Southern Medical University, Shenzhen, China

    Dinglan Wu

Authors
  1. Sin Ting Chow
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jiaqi Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xingxing Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuliang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Youjia Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chi-Fai Ng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaojuan Pei
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Qingyou Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Fei Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Dinglan Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Franky Leung Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

STC and JF performed major experiments and data analysis, and prepared manuscript; XZ, YW and YL performed experiments and plasmid construction; CFN, XP, QZ and FW provided clinical tissues and pathology analysis; DW and FLC conceived research and experiments, acquired research funds, wrote and edited manuscript. All authors approved the final version of the manuscript.

Corresponding authors

Correspondence to Dinglan Wu or Franky Leung Chan.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

All animal procedures were performed in accordance with the institutional laboratory animal guidelines and with approval from the animal experimentation ethics committee of The Chinese University of Hong Kong (Ref. No. 18-002-GRF). The use of human prostate cancer tissues for primary cultures was with prior informed consent from patients and was approved by the Joint Chinese University of Hong Kong- New Territories East Cluster Clinical Research Ethics Committee (Ref. No. CRE-2010.579).

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chow, S.T., Fan, J., Zhang, X. et al. Nuclear receptor TLX functions to promote cancer stemness and EMT in prostate cancer via its direct transactivation of CD44 and stem cell-regulatory transcription factors. Br J Cancer (2024). https://doi.org/10.1038/s41416-024-02843-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41416-024-02843-z

Search

Advanced search

Quick links