Tumor protein D52 (isoform 3) contributes to prostate cancer cell growth via targeting nuclear factor-κB transactivation in LNCaP cells

Abstract

Our previous study showed that TPD52 overexpression could increase migration and proliferation of LNCaP cells contributing to the development of prostate cancer. However, mechanism of TPD52 in prostate cancer initiation and progression remains elusive. In this study, we investigated the possible underlying mechanism of TPD52 in prostate cancer progression. In LNCaP cells, TPD52 expression was altered by transfecting with either EGFP-TPD52 or specific short hairpin RNA. Overexpression of TPD52 protected LNCaP cells from apoptosis through elevated anti-apoptotic proteins XIAP, Bcl-2, and Cyclin D1, whereas Bax was downregulated. Mechanistically, we found that TPD52 confers transactivation of nuclear factor-κB, thereby enhancing its target gene expression in LNCaP cells. TPD52 promotes LNCaP cell invasion probably via increased matrix metalloproteinase 9 expression and its activity while tissue inhibitor of metalloproteinase expression is significantly downregulated. Notably, TPD52 might be involved in cell adhesion, promoting tumor metastasis by inducing loss of E-cadherin, expression of vimentin and vascular cell adhesion molecule, and additionally activation of focal adhesion kinase. Furthermore, TPD52 directly interacts with nuclear factor-κB p65 (RelA) and promotes accumulation of phosphorylated nuclear factor-κB (p65) S536 that is directly linked with nuclear factor-κB transactivation. Indeed, depletion of TPD52 or inhibition of nuclear factor-κB in TPD52-positive cells inhibited secretion of tumor-related cytokines and contributes to the activation of STAT3, nuclear factor-κB, and Akt. Interestingly, in TPD52 overexpressing LNCaP cells, nuclear factor-κB inhibition prevented the autocrine/paracrine activation of STAT3. TPD52 activates STAT3 through ascertaining a cross talk between the nuclear factor-κB and the STAT3 signaling systems. Collectively, these results reveal mechanism by which TPD52 is associated with prostate cancer progression and highlight the approach for therapeutic targeting of TPD52 in prostate cancer.

Exosomal Circ-XIAP Promotes Docetaxel Resistance in Prostate Cancer by Regulating miR-1182/TPD52 Axis

“…Tumor protein D52 (TPD52), a chromosome 8q21 amplification target, acts as an oncogene in many cancers, including PCa. 25,26 Coincidently, by bioinformatics analysis, we found that both circ-XIAP and 3ʹUTR of TPD52 had the complementary binding sequence for miR-1182, which suggested the interactions among circ-XIAP, miR-1182 and TPD52 in DTX resistance of PCa.…”

MicroRNA‑379 suppresses cell proliferation, migration and invasion in nasopharyngeal carcinoma by targeting tumor protein D52

“…In addition, overexpression of miR-379 reduced TPD52 mRNA and protein expression levels, suggesting that miR-379 negatively regulated the TPD52 protein synthesis though degradation of the mRNA. Recently, a previous study revealed that elevated TPD52 levels may promote the migration and proliferation of prostate cancer LNCaP cells though activation of nuclear factor-κB signaling ( 34 ). Consistently, the present study observed that the knockdown of TPD52 was able to inhibit the growth, migration and invasion of NPC cells.…”

Tumor protein D54 defines a new class of intracellular transport vesicles

“…However, all members have been found to be overexpressed in a series of cancers (Cao et al, 2006;Byrne et al, 1995Byrne et al, , 1998Nourse et al, 1998). Overexpression of TPD52 correlates with poor prognosis in breast cancer patients, and in cell models, TPD52 overexpression promotes proliferation and invasion (Byrne et al, 2010(Byrne et al, , 1996Li et al, 2017;Dasari et al, 2017).…”