Homeobox protein VentX induces p53-independent apoptosis in cancer cells

Gao, Hong; Wu, Bin; Le, Yi; Zhu, Zhongqi

doi:10.18632/oncotarget.9238

Cited by 11 publications

(9 citation statements)

References 29 publications

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“…Apoptotic activity can be reflected by the ratio of Bcl-2/Bax (24). The nuclear enzyme poly(ADP-ribose) polymerase (PARP) is a key modulator of the apoptotic pathway, which can be proteolytically cleaved by caspase-3/7 when cell apoptosis occurs (35). In the present study, C646 treatment decreased the ratio of Bcl-2/Bax in the 5 GC cell lines.…”

Section: Discussionmentioning

confidence: 50%

Histone acetyltransferase p300/CBP inhibitor C646 blocks the survival and invasion pathways of gastric cancer cell lines

Wang

Meng

et al. 2017

International Journal of Oncology

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The histone acetyltransferases (HATs) adenovirus E1A-associated protein (p300) and CREB binding protein (CBP) serve as coactivators during a diverse assortment of cellular processes. In the present study, p300 and CBP were highly expressed in 5 gastric cancer (GC) cell lines (SGC‑7901, MKN45, MGC-803, BGC-823 and KATO III) compared with human normal gastric epithelial cell line (GES-1). C646, a selective inhibitor of p300 and CBP, inhibited cell viability and cell cycle and promoted cell apoptosis in all 5 GC cell lines. In addition, C646 suppressed the migration and invasion capability of the GC cell lines, except for the middle-differentiated SGC-7901 cell line. Furthermore, we detected the differential expression of corresponding oncogenic signalling molecules, such as c-Met, Akt, Bcl-2, Bax, cyclin D1, MMP7 and MMP9, in GC cells following C646 treatment. In conclusion, our results suggest that C646 inhibits the acetylation of histone H3 via inactivation of p300 and CBP, resulting in antineoplastic effects toward GC cells. Thus, the selective HAT inhibitor C646 could be a promising antitumour reagent for GC treatment.

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Section: Discussionmentioning

confidence: 50%

Histone acetyltransferase p300/CBP inhibitor C646 blocks the survival and invasion pathways of gastric cancer cell lines

Wang

Meng

et al. 2017

International Journal of Oncology

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“…It is the first report of aberrant expression of VENTX, as a member of BMP signaling as well as a homeobox gene, in ESCC and its correlation with SALL4 as a stemness marker. VENTX is introduced as a tumor suppressor gene in colon and lung cancers . Through the progression of stages of the tumors, tumor invasion and tumor cell metastasis to the lymph nodes in ESCC, the expression of VENTX was significantly correlated with SALL4 , which suggests an oncogenic role for VENTX in ESCC progression and metastasis through correlation with stemness state regulator SALL4 .…”

Section: Discussionmentioning

confidence: 98%

Correlation between SALL4 stemness marker and bone morphogenetic protein signaling genes in esophageal squamous cell carcinoma

Assarnia

Khales

Forghanifard

2018

J Biochem & Molecular Tox

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SALL4, as a stemness marker, plays a key role in the maintenance of pluripotency and self‐renewal of cancer stem cells. To elucidate probable linkage between SALL4 stemness marker and bone morphogenetic protein (BMP) cell signaling pathway, we aimed to analyze the expression levels of the related genes in esophageal squamous cell carcinoma (ESCC) patients. Tumoral and corresponding margin normal tissues from 50 treatment‐naive ESCC patients were subjected for expression analysis using relative comparative real‐time reverse transcription polymerase chain reaction. There were significant correlations between SALL4 mRNA and BMP signaling target genes expression including SIZN1, VENTX, and DIDO1 (P < 0.01). Tight associations of gene expression were observed in primary stages of tumor progression (stages I/II), and the invaded tumors to the adventitia (T3/T4). Furthermore, significant correlations between the expression of BMP signaling target genes were observed (P < 0.01). SALL4 may play role in tumorigenesis and tumor cell invasiveness of ESCC through correlation with BMP signaling genes.

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“…Nevertheless, whether these factors can be targeted to turn TAMs into a tumoricidal cells remains unclear. As a unique human hematopoietic transcriptional factor that does not have a murine homolog, VentX was found to have essential role in controlling proliferation and differentiation of hematopoietic cells and function as a p53-independent tumor suppressor 12 , 15 , 16 , 38 – 40 . Data of our current study suggested VentX controls TAM plasticity, which in turn, reverts immune suppression at the TME through regulating TIL differentiation and function, which was supported by both in vitro and in vivo studies (Figs.…”

Section: Discussionmentioning

confidence: 99%

The homeobox protein VentX reverts immune suppression in the tumor microenvironment

Gao

Bleday

et al. 2018

Nat Commun

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Immune suppression in the tumor microenvironment (TME) is a central obstacle to effective immunotherapy. Tumor-associated macrophages (TAMs) are key components of the TME. Although TAMs have been viewed as an ideal target of intervention to steer immunity in cancer treatment, the approach has been hampered by the lack of knowledge of how TAM plasticity is controlled by cell intrinsic factors. VentX is a homeobox protein implicated in proliferation and differentiation of human hematopoietic and immune cells. Using clinical samples obtained from cancer patients, we find that VentX expression is drastically reduced in TAMs. We show here that VentX promotes M1 differentiation of TAMs, and that VentX-regulated TAMs, in turn, revert immune suppression at the TME. Using a NSG mouse model of human colon cancers, we demonstrate that VentX regulates TAM function in tumorigenesis in vivo. Our findings suggest a mechanism underlying immune suppression at TME and potential applications of VentX-regulated TAMs in cancer immunotherapy.

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Homeobox protein VentX induces p53-independent apoptosis in cancer cells

Cited by 11 publications

References 29 publications

Histone acetyltransferase p300/CBP inhibitor C646 blocks the survival and invasion pathways of gastric cancer cell lines

Histone acetyltransferase p300/CBP inhibitor C646 blocks the survival and invasion pathways of gastric cancer cell lines

Correlation between SALL4 stemness marker and bone morphogenetic protein signaling genes in esophageal squamous cell carcinoma

The homeobox protein VentX reverts immune suppression in the tumor microenvironment

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