Silencing of 14-3-3ζ over-expression in hepatocellular carcinoma inhibits tumor growth and enhances chemosensitivity to cis-diammined dichloridoplatium

Choi, Jung Eun; Hur, Wonhee; Jung, Chan Kwon; Piao, Lian Shu; Lyoo, Kwang‐Soo; Hong, Sung Woo; Kim, Sung Woo; Yoon, Hye-Yeon; Yoon, Seung Kew

doi:10.1016/j.canlet.2011.01.015

Cited by 48 publications

(61 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transient blockade of 14-3-3zeta expression by small interfering RNA (siRNA) in cancer cells effectively reduces the onset and growth of tumor xenografts in vivo. [13][14][15]20,21,27,34,43 In the cancer cells, 14-3-3zeta is commonly associated with some pro-apoptotic proteins upon phosphorylation with survival-mediating kinases, such as Akt. Phosphorylation of 14-3-3zeta by c-Jun N-terminal kinase releases the proapoptotic proteins Bad and FOXO3a from 14-3-3zeta, and antagonizes the effects of Akt signaling.…”

Section: Cell Survival and Apoptosismentioning

confidence: 99%

“…Phosphorylation of 14-3-3zeta by c-Jun N-terminal kinase releases the proapoptotic proteins Bad and FOXO3a from 14-3-3zeta, and antagonizes the effects of Akt signaling. 21,[44][45][46] As a result of dissociation, Bad is dephosphorylated and translocates to the mitochondria, where it associates with Bcl-2/Bcl-x(L), promoting apoptosis via the mitochondrial apoptotic pathway, including cytochrome c release and procaspase-9 cleavage.…”

Section: Cell Survival and Apoptosismentioning

confidence: 99%

“…70 14-3-3zeta knockdown by siRNA sensitizes cells to stressinduced apoptosis and effectively reduces the onset and growth of tumor in multiple cancer types. 13,14,21,40,63,65,71 However, the clinical application of siRNA put this approach into a dilemma for therapy targeting 14-3-3zeta. The convection-enhanced delivery of siRNA (or shorthairpin RNA, adenovirus and so on) provides a new technique to neuro-system cancer treatment.…”

Section: Rnaimentioning

confidence: 99%

“…13 The importance of 14-3-3zeta in the formation and progression of cancer has been emphasized within several tumor types. [14][15][16][17][18][19][20][21][22][23][24] In this review, we will investigate the role of 14-3-3zeta in cancer and suggest a new target in anticancer therapy.…”

Section: Introductionmentioning

confidence: 99%

“…Sometimes, cytoplasmic and nuclear expression is observed even in the same tissue. 19 14-3-3zeta-positive expression occurs in the lung cancer, [25][26][27][28] liver cancer, 21 uterus, breast carcinoma, 14 stomach cancer, 29 head and neck squamous cell carcinoma 15 and so on. In addition, 14-3-3zeta protein expression is elevated in the breast cancer, 14 36 which shows 14-3-3zeta overexpression also occurred in cervical, ovarian, skin, pancreatic, prostate and urothelial tumors.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Targeting 14-3-3zeta in cancer therapy

et al. 2011

View full text Add to dashboard Cite

Section: Cell Survival and Apoptosismentioning

confidence: 99%

Section: Cell Survival and Apoptosismentioning

confidence: 99%

Section: Rnaimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Targeting 14-3-3zeta in cancer therapy

et al. 2011

View full text Add to dashboard Cite

14‐3‐3ζ binds to hepatitis B virus protein X and maintains its protein stability in hepatocellular carcinoma cells

et al. 2018

View full text Add to dashboard Cite

Abstract14‐3‐3ζ, a phosphopeptide‐binding molecule, is reportedly overexpressed in the cancerous tissues of patients with hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) protein X (HBx) draws intensive attention in HBV‐related HCC because it not only regulates HBV replication, but also promotes carcinogenesis by interacting with various tumor or antitumor molecules. This study is performed to investigate whether and how 14‐3‐3ζ interacts with HBx. The coimmunoprecipitation (Co‐IP) results showed that 14‐3‐3ζ bond to HBx in HBV‐infected Hep3B HCC cells and CSQT‐2 portal vein tumor thrombosis (PVTT) cells. By performing Co‐IP assay in HBV‐free Huh7 cells expressing wild‐type HBx, mutant HBx‐S31A, or HBx‐S31D (serine31 was mutated into alanine31 or aspartic acid31), we found that the phosphorylated serine31 with its near amino acid residues constituted a RPLphosphoS31 GP (R, arginine; P, proline; L, leucine; S, serine; G, glycine) motif in HBx for 14‐3‐3ζ docking. This 14‐3‐3ζ‐HBx interaction was partly impaired when Akt signaling transduction was blocked by LY294002. Furthermore, 14‐3‐3ζ silencing augmented HBx ubiquitination and decreased its expression in cancer cells and xenograft tumor. The migratory and invasive abilities of CSQT‐2 cells were inhibited upon 14‐3‐3ζ silencing, whereas partly restored by HBx overexpression. Additionally, 14‐3‐3ζ positively correlated with HBx to be overexpressed in the primary HCC tissues (r = 0.344) and metastatic PVTT (r = 0.348). In summary, findings of this study reveal a novel 14‐3‐3ζ‐HBx interaction in HCC cells and suggest 14‐3‐3ζ as a candidate target for treating HBV‐related HCC.

show abstract