Knockdown of TACC3 inhibits tumor cell proliferation and increases chemosensitivity in pancreatic cancer.
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
27 Nov 2023
27 Nov 2023
Historique:
received:
09
07
2023
accepted:
15
11
2023
revised:
06
11
2023
medline:
29
11
2023
pubmed:
28
11
2023
entrez:
27
11
2023
Statut:
epublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant digestive tract tumor with limited clinical treatments. Transforming acidic coiled-coil-containing protein 3 (TACC3) is a component of the centrosome axis and a member of the TACC family, which affect mitosis and regulate chromosome stability and are involved in tumor development and progression. However, the role of TACC3 in PDAC remains elusive. In this study, by exploiting the TCGA database, we found that high TACC3 expression in PDAC is associated with poor prognosis. shRNA-mediated TACC3 knockdown caused S phase arrest of the cell cycle and inhibited proliferation in PDAC cell lines. Through RNA sequencing and protein co-immunoprecipitation combined with mass spectrometry, KIF11 was identified as a protein that interacts with TACC3. TACC3 stabilizes and regulates KIF11 protein expression levels in PDAC cells through physical interaction. Knockdown of TACC3 or KIF11 resulted in abnormal spindle formation during cell division both in vitro and in vivo. Pharmacological inhibition of TACC3 or KIF11 can suppress tumor cell proliferation and promote apoptosis. Our studies further demonstrated that high expression of TACC3 and KIF11 mediated the resistance of PDAC to gemcitabine, and deficiency of TACC3 or KIF11 increased the sensitivity of PDAC cells to chemotherapy. In conclusion, our study reveals the fundamental role of TACC3 expression in PDAC cell proliferation and chemoresistance, suggesting that TACC3 can be used as a molecular marker to evaluate the prognosis of PDAC.
Identifiants
pubmed: 38012214
doi: 10.1038/s41419-023-06313-x
pii: 10.1038/s41419-023-06313-x
pmc: PMC10682013
doi:
Substances chimiques
Cell Cycle Proteins
0
Microtubule-Associated Proteins
0
TACC3 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
778Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82303646
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 82173091
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 81701630
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : U21A20374
Informations de copyright
© 2023. The Author(s).
Références
Cold Spring Harb Perspect Biol. 2015 Aug 03;7(8):a005959
pubmed: 26238352
EMBO J. 2020 Jan 15;39(2):e102378
pubmed: 31782546
CA Cancer J Clin. 2022 Jan;72(1):7-33
pubmed: 35020204
J Hematol Oncol. 2021 Sep 16;14(1):148
pubmed: 34530889
Cancer Res. 2017 Jun 1;77(11):3092-3100
pubmed: 28377455
Cell Signal. 2022 Apr;92:110267
pubmed: 35108639
Cell Stem Cell. 2020 Jul 2;27(1):64-80.e9
pubmed: 32402250
Clin Orthop Relat Res. 2018 Sep;476(9):1848-1855
pubmed: 30024460
Science. 1995 Jun 23;268(5218):1766-9
pubmed: 7792603
Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16542-7
pubmed: 20823227
Science. 2019 Jun 28;364(6447):
pubmed: 31249032
Eur J Cancer. 2009 Jan;45(2):228-47
pubmed: 19097774
Eur J Med Chem. 2022 Dec 15;244:114874
pubmed: 36332551
Science. 2022 Nov 18;378(6621):eabq7361
pubmed: 36395215
Oncogene. 2022 Jun;41(23):3186-3196
pubmed: 35501464
Front Genet. 2021 Jun 03;12:640078
pubmed: 34149795
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Int J Cancer. 2018 Dec 15;143(12):3143-3154
pubmed: 29978472
JAMA Surg. 2020 Sep 1;155(9):832-839
pubmed: 32667641
Cell Mol Biol Lett. 2022 Oct 11;27(1):90
pubmed: 36221072
ACS Chem Biol. 2013 Mar 15;8(3):626-35
pubmed: 23240775
Cell Res. 2020 Sep;30(9):779-793
pubmed: 32296111
AJR Am J Roentgenol. 2010 Aug;195(2):281-9
pubmed: 20651182
Semin Cell Dev Biol. 2010 May;21(3):255-9
pubmed: 20109572
Cell Rep. 2022 May 10;39(6):110813
pubmed: 35545048
Mol Cancer Res. 2021 Oct;19(10):1651-1665
pubmed: 34158391
Semin Cell Dev Biol. 2014 Jul;31:20-9
pubmed: 24727350
Nat Rev Mol Cell Biol. 2017 Mar;18(3):187-201
pubmed: 28174430
Acta Pharmacol Sin. 2011 Dec;32(12):1543-8
pubmed: 21986572
Annu Rev Biophys. 2016 Jul 5;45:279-98
pubmed: 27145873
Ann Surg. 2021 Apr 1;273(4):806-813
pubmed: 31274655
EMBO Rep. 2013 Sep;14(9):829-36
pubmed: 23887685
Lancet. 2020 Jun 27;395(10242):2008-2020
pubmed: 32593337
Curr Gene Ther. 2016;16(3):156-67
pubmed: 27216914
J Natl Compr Canc Netw. 2021 Apr 1;19(4):439-457
pubmed: 33845462
PLoS One. 2015 Dec 28;10(12):e0144969
pubmed: 26709920
Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11318-23
pubmed: 11572983
Signal Transduct Target Ther. 2023 Apr 7;8(1):142
pubmed: 37024477
J Ginseng Res. 2022 Sep;46(5):636-645
pubmed: 36090681
Oncol Rep. 1999 Sep-Oct;6(5):1117-22
pubmed: 10425312
Biochem Biophys Res Commun. 2017 May 13;486(4):872-878
pubmed: 28336437
Trends Biochem Sci. 2016 Oct;41(10):824-833
pubmed: 27469524
J Exp Clin Cancer Res. 2017 Aug 10;36(1):107
pubmed: 28797284
Appl Immunohistochem Mol Morphol. 2018 Feb;26(2):113-119
pubmed: 27258563
Annu Rev Biochem. 2016 Jun 2;85:659-83
pubmed: 27145846
Annu Rev Cell Dev Biol. 1997;13:83-117
pubmed: 9442869
Nat Rev Gastroenterol Hepatol. 2018 Jun;15(6):333-348
pubmed: 29717230
Nat Cell Biol. 2007 Mar;9(3):299-309
pubmed: 17310241
Cell Death Dis. 2022 Oct 25;13(10):896
pubmed: 36280663
Cells. 2020 Oct 26;9(11):
pubmed: 33114575
Nat Commun. 2016 Aug 05;7:12355
pubmed: 27492783
Signal Transduct Target Ther. 2023 Mar 1;8(1):92
pubmed: 36859359
Neoplasia. 2014 Dec;16(12):1082-93
pubmed: 25499221
Front Biosci (Landmark Ed). 2022 Aug 30;27(8):252
pubmed: 36042187
Exp Cell Res. 2020 May 15;390(2):111952
pubmed: 32156598
ACS Chem Biol. 2017 Apr 21;12(4):1038-1046
pubmed: 28165699
Med Oncol. 2022 Jun 18;39(9):124
pubmed: 35716217
J Natl Compr Canc Netw. 2019 May 1;17(5.5):603-605
pubmed: 31117041
Int J Lab Hematol. 2020 Dec;42(6):842-848
pubmed: 32744749
Proc Natl Acad Sci U S A. 2013 Sep 17;110(38):15295-300
pubmed: 24003142
Biochem Biophys Res Commun. 2018 Apr 15;498(4):1085-1092
pubmed: 29555478
Phytomedicine. 2020 Jan;66:153112
pubmed: 31786318
Cancer Lett. 2021 May 28;506:1-10
pubmed: 33652084