Downregulation of STRAP promotes tumor growth and metastasis in hepatocellular carcinoma via reducing PTEN level

被引:9
作者
Wu, Qiong [1 ]
Yu, Shijun [1 ]
Chen, Jingde [1 ]
Li, Yandong [1 ,2 ]
Gao, Yong [1 ]
机构
[1] Tongji Univ, Shanghai East Hosp, Dept Oncol, Sch Med, 150 Ji Mo Rd, Shanghai 200120, Peoples R China
[2] Tongji Univ, Shanghai East Hosp, Res Ctr Translat Med, Sch Med, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
STRAP; PTEN; hepatocellular carcinoma; tumor growth; metastasis; TGF-BETA; PROTEIN; CANCER; MAWD; SUPPRESSOR; STABILITY; P53;
D O I
10.1002/iub.1707
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The serine-threonine kinase receptor-associated protein (STRAP) has been implicated in multiple human cancers. However, its expression and function are currently unclear and controversial in different tissue types. In the present study, we report that aberrant downregulation of STRAP in hepatocellular carcinoma (HCC) facilitated tumor cell growth and metastasis in a phosphatase and tensin homologue (PTEN)-dependent manner. Immunohistochemical analysis and quantitative real-time polymerase chain reaction results indicated that STRAP was frequently downregulated in HCC samples. Functionally, knockdown of STRAP by RNA inference in HCC cells promoted proliferation and migration in vitro and tumorigenicity and lung metastasis in vivo. Through detecting the expression of some tumor-related genes using western blot analysis, we found the tumor suppressor PTEN was decreased upon STRAP silencing. Further analyses demonstrated that silenced STRAP led to PTEN protein degradation. Immunohistochemical analysis revealed that STRAP expression was closely associated with PTEN expression in 30 cases of HCC samples. These findings strongly suggest that STRAP plays an inhibitory role in HCC via regulating PTEN expression and could be a potential therapeutic target for this disease. (c) 2017 IUBMB Life, 70(2):120-128, 2018
引用
收藏
页码:120 / 128
页数:9
相关论文
共 28 条
  • [1] [Anonymous], MOL CELL BI IN PRESS
  • [2] STRAP is a strong predictive marker of adjuvant chemotherapy benefit in colorectal cancer
    Buess, M
    Terracciano, L
    Reuter, J
    Ballabeni, P
    Boulay, JL
    Laffer, U
    Metzger, U
    Herrmann, R
    Rochlitz, C
    [J]. NEOPLASIA, 2004, 6 (06): : 813 - 820
  • [3] Enzymatic Analysis of PTEN Ubiquitylation by WWP2 and NEDD4-1 E3 Ligases
    Chen, Zan
    Thomas, Stefani N.
    Bolduc, David M.
    Jiang, Xuejun
    Zhang, Xiangbin
    Wolberger, Cynthia
    Cole, Philip A.
    [J]. BIOCHEMISTRY, 2016, 55 (26) : 3658 - 3666
  • [4] STRAP and Smad7 synergize in the inhibition of transforming growth factor β signaling
    Datta, PK
    Moses, HL
    [J]. MOLECULAR AND CELLULAR BIOLOGY, 2000, 20 (09) : 3157 - 3167
  • [5] Identification of STRAP, a novel WD domain protein in transforming growth factor-β signaling
    Datta, PK
    Chytil, A
    Gorska, AE
    Moses, HL
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (52) : 34671 - 34674
  • [6] PTEN Protein Loss and Clinical Outcome from Castration-resistant Prostate Cancer Treated with Abiraterone Acetate
    Ferraldeschi, Roberta
    Rodrigues, Daniel Nava
    Riisnaes, Ruth
    Miranda, Susana
    Figueiredo, Ines
    Rescigno, Pasquale
    Ravi, Praful
    Pezaro, Carmel
    Omlin, Aurelius
    Lorente, David
    Zafeiriou, Zafeiris
    Mateo, Joaquin
    Altavilla, Amelia
    Sideris, Spyridon
    Bianchini, Diletta
    Grist, Emily
    Thway, Khin
    Lopez, Raquel Perez
    Tunariu, Nina
    Parker, Chris
    Dearnaley, David
    Reid, Alison
    Attard, Gerhardt
    de Bono, Johann
    [J]. EUROPEAN UROLOGY, 2015, 67 (04) : 795 - 802
  • [7] Oncogenic function of a novel WD-domain protein, STRAP, in human carcinogenesis
    Haider, Sunil K.
    Anumanthan, Govindaraj
    Maddula, Ramakoti
    Mann, Jason
    Chytil, Anna
    Gonzalez, Adriana L.
    Washington, M. Key
    Moses, Harold L.
    Beauchamp, R. Daniel
    Datta, Pran K.
    [J]. CANCER RESEARCH, 2006, 66 (12) : 6156 - 6166
  • [8] STRAP Acts as a Scaffolding Protein in Controlling the TLR2/4 Signaling Pathway
    Huh, Hyunbin D.
    Ra, Eun A.
    Lee, Taeyun A.
    Kang, Sujin
    Park, Areum
    Lee, Eunhye
    Choi, Junhee L.
    Jang, Eunji
    Lee, Ji Eun
    Lee, Sungwook
    Park, Boyoun
    [J]. SCIENTIFIC REPORTS, 2016, 6
  • [9] STRAP Promotes Stemness of Human Colorectal Cancer via Epigenetic Regulation of the NOTCH Pathway
    Jin, Lin
    Trung Vu
    Yuan, Guandou
    Datta, Pran K.
    [J]. CANCER RESEARCH, 2017, 77 (20) : 5464 - 5478
  • [10] Oncogenic STRAP functions as a novel negative regulator of E-cadherin and p21Cip1 by modulating the transcription factor Sp1
    Jin, Lin
    Datta, Pran K.
    [J]. CELL CYCLE, 2014, 13 (24) : 3909 - 3920