Nuclear receptor coactivator SRC-1 promotes colorectal cancer progression through enhancing GLI2-mediated Hedgehog signaling.
Animals
Carcinogenesis
/ genetics
Cell Proliferation
/ genetics
Colorectal Neoplasms
/ genetics
Gene Expression Regulation, Neoplastic
Hedgehog Proteins
/ metabolism
Humans
Mice
Nuclear Proteins
/ genetics
Nuclear Receptor Coactivator 1
/ genetics
Signal Transduction
/ physiology
Zinc Finger Protein Gli2
/ metabolism
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
12
09
2021
accepted:
30
03
2022
revised:
29
03
2022
pubmed:
15
4
2022
medline:
18
5
2022
entrez:
14
4
2022
Statut:
ppublish
Résumé
Overexpression of nuclear coactivator steroid receptor coactivator 1 (SRC-1) and aberrant activation of the Hedgehog (Hh) signaling pathway are associated with various tumorigenesis; however, the significance of SRC-1 in colorectal cancer (CRC) and its contribution to the activation of Hh signaling are unclear. Here, we identified a conserved Hh signaling signature positively correlated with SRC-1 expression in CRC based on TCGA database; SRC-1 deficiency significantly inhibited the proliferation, survival, migration, invasion, and tumorigenesis of both human and mouse CRC cells, and SRC-1 knockout significantly suppressed azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CRC in mice. Mechanistically, SRC-1 promoted the expression of GLI family zinc finger 2 (GLI2), a major downstream transcription factor of Hh pathway, and cooperated with GLI2 to enhance multiple Hh-regulated oncogene expression, including Cyclin D1, Bcl-2, and Slug. Pharmacological blockages of SRC-1 and Hh signaling retarded CRC progression in human CRC cell xenograft mouse model. Together, our studies uncover an SRC-1/GLI2-regulated Hh signaling looping axis that promotes CRC tumorigenesis, offering an attractive strategy for CRC treatment.
Identifiants
pubmed: 35418691
doi: 10.1038/s41388-022-02308-8
pii: 10.1038/s41388-022-02308-8
doi:
Substances chimiques
GLI2 protein, human
0
Hedgehog Proteins
0
Nuclear Proteins
0
Zinc Finger Protein Gli2
0
NCOA1 protein, human
EC 2.3.1.48
Nuclear Receptor Coactivator 1
EC 2.3.1.48
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2846-2859Informations de copyright
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.
Références
O’Malley BW, Kumar R. Nuclear receptor coregulators in cancer biology. Cancer Res. 2009;69:8217–22.
pubmed: 19843848
pmcid: 2783444
doi: 10.1158/0008-5472.CAN-09-2223
Lonard DM, O’Malley BW. Nuclear receptor coregulators: modulators of pathology and therapeutic targets. Nat Rev Endocrinol. 2012;8:598–604.
pubmed: 22733267
pmcid: 3564250
doi: 10.1038/nrendo.2012.100
Mark M, Yoshida-Komiya H, Gehin M, Liao L, Tsai MJ, O’Malley BW, et al. Partially redundant functions of SRC-1 and TIF2 in postnatal survival and male reproduction. Proc Natl Acad Sci USA. 2004;101:4453–8.
pubmed: 15070739
pmcid: 384768
doi: 10.1073/pnas.0400234101
Xu J, Qiu Y, DeMayo FJ, Tsai SY, Tsai MJ, O’Malley BW. Partial hormone resistance in mice with disruption of the steroid receptor coactivator-1 (SRC-1) gene. Science 1998;279:1922–5.
pubmed: 9506940
doi: 10.1126/science.279.5358.1922
Picard F, Géhin M, Annicotte J, Rocchi S, Champy MF, O’Malley BW, et al. SRC-1 and TIF2 control energy balance between white and brown adipose tissues. Cell 2002;111:931–41.
pubmed: 12507421
doi: 10.1016/S0092-8674(02)01169-8
Louet JF, Chopra AR, Sagen JV, An J, York B, Tannour-Louet M, et al. The coactivator SRC-1 is an essential coordinator of hepatic glucose production. Cell Metab. 2010;12:606–18.
pubmed: 21109193
pmcid: 3024581
doi: 10.1016/j.cmet.2010.11.009
Duteil D, Chambon C, Ali F, Malivindi R, Zoll J, Kato S, et al. The transcriptional coregulators TIF2 and SRC-1 regulate energy homeostasis by modulating mitochondrial respiration in skeletal muscles. Cell Metab. 2010;12:496–508.
pubmed: 21035760
pmcid: 3032428
doi: 10.1016/j.cmet.2010.09.016
Walsh CA, Bolger JC, Byrne C, Cocchiglia S, Hao Y, Fagan A, et al. Global gene repression by the steroid receptor coactivator SRC-1 promotes oncogenesis. Cancer Res. 2014;74:2533–44.
pubmed: 24648347
doi: 10.1158/0008-5472.CAN-13-2133
Qin L, Wu YL, Toneff MJ, Li D, Liao L, Gao X, et al. NCOA1 directly targets M-CSF1 expression to promote breast cancer metastasis. Cancer Res. 2014;74:3477–88.
pubmed: 24769444
pmcid: 4083628
doi: 10.1158/0008-5472.CAN-13-2639
Wang Y, Lonard DM, Yu Y, Chow DC, Palzkill TG, O’Malley BW. Small molecule inhibition of the steroid receptor coactivators, SRC-3 and SRC-1. Mol Endocrinol. 2011;25:2041–53.
pubmed: 22053001
pmcid: 3231837
doi: 10.1210/me.2011-1222
Qin L, Chen X, Wu Y, Feng Z, He T, Wang L, et al. Steroid receptor coactivator-1 upregulates integrin α
pubmed: 21343398
pmcid: 3076137
doi: 10.1158/0008-5472.CAN-10-3453
Xu J, Wu RC, O’Malley BW. Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family. Nat Rev Cancer. 2009;9:615–30.
pubmed: 19701241
pmcid: 2908510
doi: 10.1038/nrc2695
Giudici M, Goni S, Fan R, Treuter E. Nuclear receptor coregulators in metabolism and disease. Handb Exp Pharm. 2016;233:95–135.
doi: 10.1007/164_2015_5
Kato S, Yokoyama A, Fujiki R. Nuclear receptor coregulators merge transcriptional coregulation with epigenetic regulation. Trends Biochem Sci. 2011;36:272–81.
pubmed: 21315607
doi: 10.1016/j.tibs.2011.01.001
Hsia EY, Goodson ML, Zou JX, Privalsky ML, Chen HW. Nuclear receptor coregulators as a new paradigm for therapeutic targeting. Adv Drug Deliv Rev. 2010;62:1227–37.
pubmed: 20933027
pmcid: 5004779
doi: 10.1016/j.addr.2010.09.016
Na SY, Lee SK, Han SJ, Choi HS, Im SY, Lee JW. Steroid receptor coactivator-1 interacts with the p50 subunit and coactivates nuclear factor kappaB-mediated transactivations. J Biol Chem. 1998;273:10831–4.
pubmed: 9556555
doi: 10.1074/jbc.273.18.10831
Lee SK, Kim HJ, Kim JW, Lee JW. Steroid receptor coactivator-1 and its family members differentially regulate transactivation by the tumor suppressor protein p53. Mol Endocrinol. 1999;13:1924–33.
pubmed: 10551785
doi: 10.1210/mend.13.11.0365
Myers E, Hill AD, Kelly G, McDermott EW, O’Higgins NJ, Buggy Y, et al. Associations and interactions between Ets-1 and Ets-2 and coregulatory proteins, SRC-1, AIB1, and NCoR in breast cancer. Clin Cancer Res. 2005;11:2111–22.
pubmed: 15788656
doi: 10.1158/1078-0432.CCR-04-1192
Russo L, Giller K, Pfitzner E, Griesinger C, Becker S. Insight into the molecular recognition mechanism of the coactivator NCoA1 by STAT6. Sci Rep. 2017;7:16845.
pubmed: 29203888
pmcid: 5714956
doi: 10.1038/s41598-017-17088-5
Wang S, Yuan Y, Liao L, Kuang SQ, Tien JC, O’Malley BW, et al. Disruption of the SRC-1 gene in mice suppresses breast cancer metastasis without affecting primary tumor formation. Proc Natl Acad Sci USA. 2009;106:151–6.
pubmed: 19109434
doi: 10.1073/pnas.0808703105
Qin L, Liu Z, Chen H, Xu J. The steroid receptor coactivator-1 regulates twist expression and promotes breast cancer metastasis. Cancer Res. 2009;69:3819–27.
pubmed: 19383905
pmcid: 2911143
doi: 10.1158/0008-5472.CAN-08-4389
Meerson A, Yehuda H. Leptin and insulin up-regulate miR-4443 to suppress NCOA1 and TRAF4, and decrease the invasiveness of human colon cancer cells. BMC Cancer. 2016;16:882.
pubmed: 27842582
pmcid: 5109693
doi: 10.1186/s12885-016-2938-1
Tong Z, Li M, Wang W, Mo P, Yu L, Liu K, et al. Steroid receptor coactivator 1 promotes human hepatocellular carcinoma progression by enhancing Wnt/β-Catenin signaling. J Biol Chem. 2015;290:18596–608.
pubmed: 26082485
pmcid: 4513118
doi: 10.1074/jbc.M115.640490
Walsh CA, Qin L, Tien JC, Young LS, Xu J. The function of steroid receptor coactivator-1 in normal tissues and cancer. Int J Biol Sci. 2012;8:470–85.
pubmed: 22419892
pmcid: 3303173
doi: 10.7150/ijbs.4125
Zeng X, Goetz JA, Suber LM, Scott WJ Jr., Schreiner CM, Robbins DJ. A freely diffusible form of Sonic hedgehog mediates long-range signalling. Nature. 2001;411:716–20.
pubmed: 11395778
doi: 10.1038/35079648
Briscoe J, Thérond PP. The mechanisms of Hedgehog signalling and its roles in development and disease. Nat Rev Mol Cell Biol. 2013;14:416–29.
pubmed: 23719536
doi: 10.1038/nrm3598
Zhao C, Cai S, Shin K, Lim A, Kalisky T, Lu WJ, et al. Stromal Gli2 activity coordinates a niche signaling program for mammary epithelial stem cells. Science. 2017;356.
Du K, Hyun J, Premont RT, Choi SS, Michelotti GA, Swiderska-Syn M, et al. Hedgehog-YAP signaling pathway regulates glutaminolysis to control activation of hepatic stellate cells. Gastroenterology. 2018;154:1465–79.e1413.
pubmed: 29305935
doi: 10.1053/j.gastro.2017.12.022
Sari IN, Phi LTH, Jun N, Wijaya YT, Lee S, Kwon HY. Hedgehog signaling in cancer: a prospective therapeutic target for eradicating cancer stem cells. Cells. 2018;7:208.
pmcid: 6262325
doi: 10.3390/cells7110208
Sang Y, Li Y, Song L, Alvarez AA, Zhang W, Lv D, et al. TRIM59 promotes gliomagenesis by inhibiting TC45 dephosphorylation of STAT3. Cancer Res. 2018;78:1792–804.
pubmed: 29386185
pmcid: 5882560
doi: 10.1158/0008-5472.CAN-17-2774
Raleigh DR, Choksi PK, Krup AL, Mayer W, Santos N, Reiter JF. Hedgehog signaling drives medulloblastoma growth via CDK6. J Clin Invest. 2018;128:120–4.
pubmed: 29202464
doi: 10.1172/JCI92710
Fattahi S, Pilehchian Langroudi M, Akhavan-Niaki H. Hedgehog signaling pathway: epigenetic regulation and role in disease and cancer development. J Cell Physiol. 2018;233:5726–35.
pubmed: 29380372
doi: 10.1002/jcp.26506
Zeng X, Ju D. Hedgehog signaling pathway and autophagy in cancer. Int J Mol Sci. 2018;19:2279.
pmcid: 6121518
doi: 10.3390/ijms19082279
Papadopoulos V, Tsapakidis K, Riobo Del Galdo NA, Papandreou CN, Del Galdo F, Anthoney A, et al. The prognostic significance of the hedgehog signaling pathway in colorectal cancer. Clin Colorectal Cancer. 2016;15:116–27.
pubmed: 27032873
doi: 10.1016/j.clcc.2016.02.010
Kangwan N, Kim YJ, Han YM, Jeong M, Park JM, Go EJ, et al. Sonic hedgehog inhibitors prevent colitis-associated cancer via orchestrated mechanisms of IL-6/gp130 inhibition, 15-PGDH induction, Bcl-2 abrogation, and tumorsphere inhibition. Oncotarget 2016;7:7667–82.
pubmed: 26716648
doi: 10.18632/oncotarget.6765
Vasaikar SV, Straub P, Wang J, Zhang B. LinkedOmics: analyzing multi-omics data within and across 32 cancer types. Nucleic Acids Res. 2018;46:D956–63.
pubmed: 29136207
doi: 10.1093/nar/gkx1090
Xu J, Li Q. Review of the in vivo functions of the p160 steroid receptor coactivator family. Mol Endocrinol. 2003;17:1681–92.
pubmed: 12805412
doi: 10.1210/me.2003-0116
Hui CC, Angers S. Gli proteins in development and disease. Annu Rev Cell Dev Biol. 2011;27:513–37.
pubmed: 21801010
doi: 10.1146/annurev-cellbio-092910-154048
Wang Y, Lonard DM, Yu Y, Chow DC, Palzkill TG, Wang J, et al. Bufalin is a potent small-molecule inhibitor of the steroid receptor coactivators SRC-3 and SRC-1. Cancer Res. 2014;74:1506–17.
pubmed: 24390736
pmcid: 3947477
doi: 10.1158/0008-5472.CAN-13-2939
Dlugosz A, Agrawal S, Kirkpatrick P. Vismodegib. Nat Rev Drug Disco. 2012;11:437–8.
doi: 10.1038/nrd3753
Chen Q, Zhuang S, Hong Y, Yang L, Guo P, Mo P, et al. Demethylase JMJD2D induces PD-L1 expression to promote colorectal cancer immune escape by enhancing IFNGR1-STAT3-IRF1 signaling. Oncogene 2022;41:1421–33.
Peng K, Zhuo M, Li M, Chen Q, Mo P, Yu C. Histone demethylase JMJD2D activates HIF1 signaling pathway via multiple mechanisms to promote colorectal cancer glycolysis and progression. Oncogene 2020;39:7076–91.
pubmed: 32989255
doi: 10.1038/s41388-020-01483-w
Zhuo M, Chen W, Shang S, Guo P, Peng K, Li M, et al. Inflammation-induced JMJD2D promotes colitis recovery and colon tumorigenesis by activating Hedgehog signaling. Oncogene 2020;39:3336–53.
pubmed: 32094404
doi: 10.1038/s41388-020-1219-2
Peng K, Kou L, Yu L, Bai C, Li M, Mo P, et al. Histone demethylase JMJD2D interacts with β-Catenin to induce transcription and activate colorectal cancer cell proliferation and tumor growth in mice. Gastroenterology 2019;156:1112–26.
pubmed: 30472235
doi: 10.1053/j.gastro.2018.11.036
Madison BB, Braunstein K, Kuizon E, Portman K, Qiao XT, Gumucio DL. Epithelial hedgehog signals pattern the intestinal crypt-villus axis. Development 2005;132:279–89.
pubmed: 15590741
doi: 10.1242/dev.01576
Varnat F, Duquet A, Malerba M, Zbinden M, Mas C, Gervaz P, et al. Human colon cancer epithelial cells harbour active HEDGEHOG-GLI signalling that is essential for tumour growth, recurrence, metastasis and stem cell survival and expansion. EMBO Mol Med. 2009;1:338–51.
pubmed: 20049737
pmcid: 3378144
doi: 10.1002/emmm.200900039
Jain S, Song R, Xie J. Sonidegib: mechanism of action, pharmacology, and clinical utility for advanced basal cell carcinomas. Onco Targets Ther. 2017;10:1645–53.
pubmed: 28352196
pmcid: 5360396
doi: 10.2147/OTT.S130910
Xin M, Ji X, De La Cruz LK, Thareja S, Wang B. Strategies to target the Hedgehog signaling pathway for cancer therapy. Med Res Rev. 2018;38:870–913.
pubmed: 29315702
doi: 10.1002/med.21482
Berlin J, Bendell JC, Hart LL, Firdaus I, Gore I, Hermann RC, et al. A randomized phase II trial of vismodegib versus placebo with FOLFOX or FOLFIRI and bevacizumab in patients with previously untreated metastatic colorectal cancer. Clin Cancer Res. 2013;19:258–67.
pubmed: 23082002
doi: 10.1158/1078-0432.CCR-12-1800
Catenacci DV, Junttila MR, Karrison T, Bahary N, Horiba MN, Nattam SR, et al. Randomized Phase Ib/II study of gemcitabine plus placebo or vismodegib, a hedgehog pathway inhibitor, in patients with metastatic pancreatic cancer. J Clin Oncol. 2015;33:4284–92.
pubmed: 26527777
pmcid: 4678179
doi: 10.1200/JCO.2015.62.8719
Mo P, Zhou Q, Guan L, Wang Y, Wang W, Miao M, et al. Amplified in breast cancer 1 promotes colorectal cancer progression through enhancing notch signaling. Oncogene 2015;34:3935–45.
pubmed: 25263446
doi: 10.1038/onc.2014.324
Datta A, Biswas K, Sommers JA, Thompson H, Awate S, Nicolae CM, et al. WRN helicase safeguards deprotected replication forks in BRCA2-mutated cancer cells. Nat Commun. 2021;12:6561.
pubmed: 34772932
pmcid: 8590011
doi: 10.1038/s41467-021-26811-w
Lin J, Liu H, Fukumoto T, Zundell J, Yan Q, Tang CA, et al. Targeting the IRE1α/XBP1s pathway suppresses CARM1-expressing ovarian cancer. Nat Commun. 2021;12:5321.
pubmed: 34493732
pmcid: 8423755
doi: 10.1038/s41467-021-25684-3
Seba V, de Lima GG, Pereira BL, Silva G, Reinhardt LS, Arantes PR, et al. Development, Characterization and Cell Viability Inhibition of PVA Spheres Loaded with Doxorubicin and 4’-Amino-1-Naphthyl-Chalcone (D14) for Osteosarcoma. Polymers (Basel) 2021;13:2611.
Yu G, Wang LG, Han Y, He QY. clusterProfiler: an R package for comparing biological themes among gene clusters. Omics 2012;16:284–7.
pubmed: 22455463
pmcid: 3339379
doi: 10.1089/omi.2011.0118