Elevated HOXB9 expression promotes differentiation and predicts a favourable outcome in colon adenocarcinoma patients

Zhan, Jun; Niu, Miaomiao; Wang, Pengjie; Zhu, Xiang; Li, S; Song, Jianguo; He, Huiying; Wang, Yixiang; Xue, Lixiang; Fang, Wei‐Gang; Zhang, H

doi:10.1038/bjc.2014.387

Cited by 37 publications

(78 citation statements)

References 28 publications

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“…This observation is in accordance with HOX gene expression, including HOX9 , reported in the mouse and human placenta [110–113]. In trophoblast cells, HOXB9 could contribute to the implantation process (reviewed in [114, 115]) by promoting the epithelial-to-mesenchymal transition (EMT), angiogenesis, cell migration and invasion (mouse) through the regulation of angiogenic factors and TGF-β2 , as evidenced in cancers [47, 85–87]. Moreover, in a subset of superficial trophoblast cells from E6.5 mouse embryos, HOXB9 was observed in association with cytoplasmic vesicles.…”

Section: Discussionsupporting

confidence: 79%

“…HOXB9 might thus play a role in the control of EGA but could also regulate the very few genes that are transcribed at the earliest stages. Several genes have been shown to be directly or indirectly regulated by HOXB9 [47, 85–87] and, for some of them, are known to be expressed in oocytes and/or early embryos and could potentially act downstream of HOXB9 in such context. For example, HOXB9 is known to directly regulate TGF-β2 transcription and the TGF-β/SMAD pathway is crucial for the bidirectional communication between the oocyte and the surrounding granulosa/cumulus cells [88].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, many direct or indirect HOXB9 target genes identified in distinct contexts [47, 85–87] are expressed in TE. AMPHIREGULIN is an EGF-like peptide involved in TE cell proliferation in the mouse and pig [91, 92].…”

Section: Discussionmentioning

confidence: 99%

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Dynamic Pattern of HOXB9 Protein Localization during Oocyte Maturation and Early Embryonic Development in Mammals

et al. 2016

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BackgroundWe previously showed that the homeodomain transcription factor HOXB9 is expressed in mammalian oocytes and early embryos. However, a systematic and exhaustive study of the localization of the HOXB9 protein, and HOX proteins in general, during mammalian early embryonic development has so far never been performed.ResultsThe distribution of HOXB9 proteins in oocytes and the early embryo was characterized by immunofluorescence from the immature oocyte stage to the peri-gastrulation period in both the mouse and the bovine. HOXB9 was detected at all studied stages with a dynamic expression pattern. Its distribution was well conserved between the two species until the blastocyst stage and was mainly nuclear. From that stage on, trophoblastic cells always showed a strong nuclear staining, while the inner cell mass and the derived cell lines showed important dynamic variations both in staining intensity and in intra-cellular localization. Indeed, HOXB9 appeared to be progressively downregulated in epiblast cells and only reappeared after gastrulation had well progressed. The protein was also detected in the primitive endoderm and its derivatives with a distinctive presence in apical vacuoles of mouse visceral endoderm cells.ConclusionsTogether, these results could suggest the existence of unsuspected functions for HOXB9 during early embryonic development in mammals.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 99%

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Dynamic Pattern of HOXB9 Protein Localization during Oocyte Maturation and Early Embryonic Development in Mammals

et al. 2016

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“…Moreover, upregulation of HOXB9 in lung adenocarcinoma patients predicts poor outcomes (13). However, decreased expression of HOXB9 showed poor overall survival in colon adenocarcinoma, pancreatic ductal adenocarcinoma or gastric carcinoma patients, displaying an opposite role in cancer progression (14–17). The diverse roles of HOXB9 in different cancer types suggest that the mechanism underlying HOXB9 in cancer progression remains complicated.…”

Section: Introductionmentioning

confidence: 98%

PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6

Wan

Zhan

et al. 2016

Nucleic Acids Res

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HOXB9 is a homeobox domain-containing transcription factor, playing an important role in embryonic development and cancer progression. However, the precise post-translational modifications (PTMs) of HOXB9 and the corresponding roles are unclear. Here, we report that acetyltransferase p300/CBP-associated factor (PCAF) interacts with and acetylates HOXB9 both in vivo and in vitro. Conversely, the acetylation of HOXB9 can be reversed by deacetylase SIRT1. Furthermore, we found that HOXB9 is acetylated at lysine 27 (AcK27). Functionally, in contrast to the wild type HOXB9, AcK27-HOXB9 decreased its capacity in promoting lung cancer cell migration and tumor growth in mice. Mechanistically, AcK27-HOXB9 suppresses the transcription of its target gene Jumonji domain-containing protein 6 (JMJD6) by direct occupying the promoter of JMJD6 gene. For clinical relevance, elevated HOXB9 acetylation at K27 predicts a better prognosis in lung adenocarcinoma patients. Taken together, we identified the first PTM of HOXB9 by demonstrating that HOXB9 can be acetylated and AcK27-HOXB9 counteracts the role of the wild-type HOXB9 in regulating lung adenocarcinoma progression.

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“…Although significant progress has been made in diagnosis and treatment of colorectal cancer, invasion, metastasis, and recurrence of the disease are still challenging (2). Hence, there is an urgent need to better understand the genetic and biological characteristic of colorectal cancer, which will improve the efficacy of the treatment of this disease, including surgical techniques, chemotherapy methods, and follow-up strategies.…”

Section: Introductionmentioning

confidence: 99%

Gas1 Inhibits Metastatic and Metabolic Phenotypes in Colorectal Carcinoma

Qin

Wei

et al. 2016

Molecular Cancer Research

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Growth arrest-specific 1 (Gas1) plays a critical role in growth suppression. Previous study indicated that Gas1 was closely associated with survival in patients with colorectal cancer; however, the underlying molecular mechanism remains unclear. In this study, we sought to determine the role of Gas1 in tumorigenesis and metastasis, and elucidate the possible mechanism. First, Gas1 was determined as a negative regulator of oncogenesis and metastasis in colorectal cancer. Mechanistically, Gas1 negatively regulated the aerobic glycolysis, a process that contributed to tumor progression and metastasis by providing energy source and building blocks for macromolecule synthesis. To further consolidate the role of Gas1 in glycolysis, the impact of Gas1 in the transcription of key glycolytic enzymes for glucose utilization was examined. As expected, GLUT4, HK2, and LDHB exhibited a decreased expression pattern. Consistent with this observation, an in vivo subcutaneous xenograft mouse model also confirmed the hypothesis that Gas1 is a negative regulator of glycolysis as reflected by the decreased 18FDG uptake in PET/CT system. Moreover, Gas1 negatively regulated the AMPK/mTOR/p70S6K signaling axis, a well-established cascade that regulates malignant cancer cell behaviors including proliferation, metastasis, and aberrant cancer metabolism. In the end, it was determined that Gas1 is a transcriptional target of FOXM1, whose role in colorectal cancer has been widely studied. Taken together, these studies establish Gas1 as a negative regulator in colorectal cancer.Implications: Gas1 suppresses cell proliferation, invasion, and aerobic glycolysis of colorectal cancer both in vitro and in vivo. Mechanistically, Gas1 inhibited EMT and the Warburg effect via AMPK/mTOR/p70S6K signaling, and Gas1 itself was directly regulated by the transcription factor FOXM1.

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Elevated HOXB9 expression promotes differentiation and predicts a favourable outcome in colon adenocarcinoma patients

Cited by 37 publications

References 28 publications

Dynamic Pattern of HOXB9 Protein Localization during Oocyte Maturation and Early Embryonic Development in Mammals

Dynamic Pattern of HOXB9 Protein Localization during Oocyte Maturation and Early Embryonic Development in Mammals

PCAF-mediated acetylation of transcriptional factor HOXB9 suppresses lung adenocarcinoma progression by targeting oncogenic protein JMJD6

Gas1 Inhibits Metastatic and Metabolic Phenotypes in Colorectal Carcinoma

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