LRP16 prevents hepatocellular carcinoma progression through regulation of Wnt/β-catenin signaling

LRP16 prevents hepatocellular carcinoma progression through regulation of Wnt/β-catenin signaling Elevated LRP16expressionisassociatedwithpoorclinical outcomes in multiple malignancies. We detected LRP16 expression in hepatocellular carcinoma (HCC) and found that it was downregulated in tumor samples and HCC cell lines. In a cohort of 80 HCC patients, high level of LRP16 expression in HCC tumors was associated with well differentiation, less lymph node metastasis, and good overall survival (OS). Overexpression of LRP16 in the HepG2 and MHCC-97L cell lines increased cell apoptosis, attenuated cell proliferation, migration, and invasion ability in vitro, and drastically diminished tumor growth and metastasis in vivo. Silencing LRP16 in HCC-LM3 and SMMC-7721 cell lines showed opposite results. Microarray evaluation of tumor cells overexpressing LRP16 revealed the effects on decreased activity in the Wnt signaling pathway. These results were confirmed by qRT-PCR and Western blots. Furthermore, inhibition of Wnt signaling decreased proliferation, migration, and invasion of HCC cell lines. Mechanism conducted showed that LRP16 overexpression could prevent β-catenin from entering the nucleus. Our study demonstrated that LRP16 suppresses tumor growth in HCC by modulating Wnt/β-catenin signaling. Key messages & LRP16 was low expression in HCC tissue and cell lines. & Low expression of LRP16 in HCC was associated with poor prognosis. & LRP16 inhibits activation of the Wnt/β-catenin pathway http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Molecular Medicine Springer Journals

LRP16 prevents hepatocellular carcinoma progression through regulation of Wnt/β-catenin signaling

12 pages
Read Article

Loading next page...
 
/lp/springer_journal/lrp16-prevents-hepatocellular-carcinoma-progression-through-regulation-f6ndIqMYaI
Publisher
Springer Journals
Copyright
Copyright © 2018 by Springer-Verlag GmbH Germany, part of Springer Nature
ISSN
0946-2716
eISSN
1432-1440
DOI
10.1007/s00109-018-1639-4
Publisher site
See Article on Publisher Site

Abstract

Elevated LRP16expressionisassociatedwithpoorclinical outcomes in multiple malignancies. We detected LRP16 expression in hepatocellular carcinoma (HCC) and found that it was downregulated in tumor samples and HCC cell lines. In a cohort of 80 HCC patients, high level of LRP16 expression in HCC tumors was associated with well differentiation, less lymph node metastasis, and good overall survival (OS). Overexpression of LRP16 in the HepG2 and MHCC-97L cell lines increased cell apoptosis, attenuated cell proliferation, migration, and invasion ability in vitro, and drastically diminished tumor growth and metastasis in vivo. Silencing LRP16 in HCC-LM3 and SMMC-7721 cell lines showed opposite results. Microarray evaluation of tumor cells overexpressing LRP16 revealed the effects on decreased activity in the Wnt signaling pathway. These results were confirmed by qRT-PCR and Western blots. Furthermore, inhibition of Wnt signaling decreased proliferation, migration, and invasion of HCC cell lines. Mechanism conducted showed that LRP16 overexpression could prevent β-catenin from entering the nucleus. Our study demonstrated that LRP16 suppresses tumor growth in HCC by modulating Wnt/β-catenin signaling. Key messages & LRP16 was low expression in HCC tissue and cell lines. & Low expression of LRP16 in HCC was associated with poor prognosis. & LRP16 inhibits activation of the Wnt/β-catenin pathway

Journal

Journal of Molecular Medicine – Springer Journals

Published: May 11, 2018

References

  • The application of RACE technique to clone the full-length cDNA of a novel leukemia associated gene LRP16
    Han, WD; Yu, L; Lou, FD; Wang, QS; Zhao, Y; Shi, ZJ; Jin, HJ
  • Clinicopathological significance of LRP16 protein in 336 gastric carcinoma patients
    Li, YZ; Zhao, P; Han, WD
  • Expression and clinical significance of LRP16 gene in human breast cancer
    Liao, DX; Han, WD; Zhao, YL; Pu, YD; Mu, YM; Luo, CH; Li, XH
  • Aberrant LRP16 protein expression in primary neuroendocrine lung tumors
    Shao, Y; Li, X; Lu, Y; Liu, L; Zhao, P
  • Clinicopathological significance and prognostic value of LRP16 expression in colorectal carcinoma
    Xi, HQ; Zhao, P; Han, WD
  • Up-regulation of LRP16 mRNA by 17beta-estradiol through activation of estrogen receptor alpha (ERalpha), but not ERbeta, and promotion of human breast cancer MCF-7 cell proliferation: a preliminary report
    Han, WD; Mu, YM; Lu, XC; Xu, ZM; Li, XJ; Yu, L; Song, HJ; Li, M; Lu, JM; Zhao, YL
  • Global cancer statistics, 2012
    Torre, LA; Bray, F; Siegel, RL; Ferlay, J; Lortet-Tieulent, J; Jemal, A
  • Epidemiology of viral hepatitis and hepatocellular carcinoma
    El-Serag, HB
  • A meta-analysis of adjuvant therapy after potentially curative treatment for hepatocellular carcinoma
    Wang, J; He, XD; Yao, N; Liang, WJ; Zhang, YC
  • The DEK oncogene promotes cellular proliferation through paracrine Wnt signaling in Ron receptor-positive breast cancers
    Privette Vinnedge, LM; Benight, NM; Wagh, PK; Pease, NA; Nashu, MA; Serrano-Lopez, J; Adams, AK; Cancelas, JA; Waltz, SE; Wells, SI
  • SOX10, a novel HMG-box-containing tumor suppressor, inhibits growth and metastasis of digestive cancers by suppressing the Wnt/beta-catenin pathway
    Tong, X; Li, L; Li, X; Heng, L; Zhong, L; Su, X; Rong, R; Hu, S; Liu, W; Jia, B
  • Dickkopf 4 (DKK4) acts on Wnt/beta-catenin pathway by influencing beta-catenin in hepatocellular carcinoma
    Fatima, S; Lee, NP; Tsang, FH; Kolligs, FT; Ng, IO; Poon, RT; Fan, ST; Luk, JM
  • ICAT is a multipotent inhibitor of beta-catenin. Focus on “role for ICAT in beta-catenin-dependent nuclear signaling and cadherin functions”
    Stow, JL
  • Methylated cyclin D2 gene circulating in the blood as a prognosis predictor of hepatocellular carcinoma
    Tsutsui, M; Iizuka, N; Moribe, T; Miura, T; Kimura, N; Tamatsukuri, S; Ishitsuka, H; Fujita, Y; Hamamoto, Y; Tsunedomi, R
  • Serum Dickkopf-1 as a biomarker for the diagnosis of hepatocellular carcinoma
    Kim, SU; Park, JH; Kim, HS; Lee, JM; Lee, HG; Kim, H; Choi, SH; Baek, S; Kim, BK; Park, JY
  • AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis
    Park, J; Schlederer, M; Schreiber, M; Ice, R; Merkel, O; Bilban, M; Hofbauer, S; Kim, S; Addison, J; Zou, J
  • MicroRNA-34a regulates WNT/TCF7 signaling and inhibits bone metastasis in Ras-activated prostate cancer
    Chen, WY; Liu, SY; Chang, YS; Yin, JJ; Yeh, HL; Mouhieddine, TH; Hadadeh, O; Abou-Kheir, W; Liu, YN
  • Interaction between LRP5 and Frat1 mediates the activation of the Wnt canonical pathway
    Hay, E; Faucheu, C; Suc-Royer, I; Touitou, R; Stiot, V; Vayssiere, B; Baron, R; Roman-Roman, S; Rawadi, G
  • Inhibition of FOSL1 overexpression in antiestrogen-resistant MCF-7 cells decreases cell growth and increases vacuolization and cell death
    Pennanen, PT; Sarvilinna, NS; Toimela, T; Ylikomi, TJ
  • Frat oncoproteins act at the crossroad of canonical and noncanonical Wnt-signaling pathways
    Amerongen, R; Nawijn, MC; Lambooij, JP; Proost, N; Jonkers, J; Berns, A
  • Notch and Wnt/beta-catenin signaling pathway play important roles in activating liver cancer stem cells
    Wang, R; Sun, Q; Wang, P; Liu, M; Xiong, S; Luo, J; Huang, H; Du, Q; Geller, DA; Cheng, B
  • Next generation sequencing of HCC from European and Asian HCC cohorts. Back to p53 and Wnt/beta-catenin
    Teufel, A; Marquardt, JU; Galle, PR
  • Beta-catenin signaling and roles in liver homeostasis, injury, and tumorigenesis
    Monga, SP
  • Keratin 18 attenuates estrogen receptor alpha-mediated signaling by sequestering LRP16 in cytoplasm
    Meng, Y; Wu, Z; Yin, X; Zhao, Y; Chen, M; Si, Y; Yang, J; Fu, X; Han, W
  • Mechanism of transcriptional regulation of LRP16 gene expression by 17-beta estradiol in MCF-7 human breast cancer cells
    Zhao, YL; Han, WD; Li, Q; Mu, YM; Lu, XC; Yu, L; Song, HJ; Li, X; Lu, JM; Pan, CY
  • GC-rich promoter elements maximally confers estrogen-induced transactivation of LRP16 gene through ERalpha/Sp1 interaction in MCF-7 cells
    Han, WD; Si, YL; Zhao, YL; Li, Q; Wu, ZQ; Hao, HJ; Song, HJ
  • Estrogenically regulated LRP16 interacts with estrogen receptor alpha and enhances the receptor's transcriptional activity
    Han, WD; Zhao, YL; Meng, YG; Zang, L; Wu, ZQ; Li, Q; Si, YL; Huang, K; Ba, JM; Morinaga, H
  • LRP16 integrates into NF-kappaB transcriptional complex and is required for its functional activation
    Wu, Z; Li, Y; Li, X; Ti, D; Zhao, Y; Si, Y; Mei, Q; Zhao, P; Fu, X; Han, W
  • An LRP16-containing preassembly complex contributes to NF-kappaB activation induced by DNA double-strand breaks
    Wu, Z; Wang, C; Bai, M; Li, X; Mei, Q; Li, X; Wang, Y; Fu, X; Luo, G; Han, W
  • Colorectal cancer and canonical Wnt signalling pathway
    Moravec, M
  • Wnt/beta-catenin signaling regulated SATB1 promotes colorectal cancer tumorigenesis and progression
    Mir, R; Pradhan, SJ; Patil, P; Mulherkar, R; Galande, S
  • MiR-424-5p reversed epithelial-mesenchymal transition of anchorage-independent HCC cells by directly targeting ICAT and suppressed HCC progression
    Zhang, Y; Li, T; Guo, P; Kang, J; Wei, Q; Jia, X; Zhao, W; Huai, W; Qiu, Y; Sun, L
  • A functional connectome: regulation of Wnt/TCF-dependent transcription by pairs of pathway activators
    Freeman, J; Smith, D; Latinkic, B; Ewan, K; Samuel, L; Zollo, M; Marino, N; Tyas, L; Jones, N; Dale, TC
  • Wnt signaling and hepatocarcinogenesis: molecular targets for the development of innovative anticancer drugs
    Pez, F; Lopez, A; Kim, M; Wands, JR; Caron de Fromentel, C; Merle, P
  • Wnt/beta-catenin signaling plays an ever-expanding role in stem cell self-renewal, tumorigenesis and cancer chemoresistance
    Mohammed, MK; Shao, C; Wang, J; Wei, Q; Wang, X; Collier, Z; Tang, S; Liu, H; Zhang, F; Huang, J
  • KIF3A binds to beta-arrestin for suppressing Wnt/beta-catenin signalling independently of primary cilia in lung cancer
    Kim, M; Suh, YA; Oh, JH; Lee, BR; Kim, J; Jang, SJ
  • ASPP2 controls epithelial plasticity and inhibits metastasis through beta-catenin-dependent regulation of ZEB1
    Wang, Y; Bu, F; Royer, C; Serres, S; Larkin, JR; Soto, MS; Sibson, NR; Salter, V; Fritzsche, F; Turnquist, C

You’re reading a free preview. Subscribe to read the entire article.

Try 2 weeks free now

DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

or browse the journals available

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off

Sign up
for free
Start 14 day
Free Trial