The helicase‐like transcription factor is a strong predictor of recurrence in hypopharyngeal but not in laryngeal squamous cell carcinomas

Capouillez, Aurélie; Debauve, Gaël; Decaestecker, Christine; Filleul, Olivier; Chevalier, Dominique; Mortuaire, G.; Coppée, Frederic; Leroy, Xavier; Belayew, Alexandra; Saussez, Sven

doi:10.1111/j.1365-2559.2009.03330.x

Cited by 20 publications

(23 citation statements)

References 29 publications

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“…Although the nature of the immunodetected proteins was not investigated in that study, we suggest that truncated forms rather than wt HLTF were expressed in the positive tumor buds because estrogens favor HLTF mRNA splicing, which leads to the synthesis of the truncated proteins [6]. These shorter forms progressively replace wt HLTF during carcinogenesis in human cervical and hypopharyngeal cancers [10,14,15]. This switch from wt to truncated HTLF forms is also linked to a poor patient prognosis.…”

Section: Discussionmentioning

confidence: 86%

“…1) [9]. In addition, alternative pre-mRNA splicing in the exons 19-22 region generates two reading frameshifts, which result in truncated protein forms [14]. Considering both translation start sites and splicing events, six different protein forms could be produced from the HLTF gene (Fig.…”

Section: Hltf Proteinsmentioning

confidence: 99%

“…1) and progressively replace wild-type HLTF during the head and neck or cervix oncogenic processes (Table 4). In head and neck cancers, Capouillez et al [10,14] focused on hypopharyngeal squamous cell carcinoma (HSCC) and laryngeal SCC (LSCC). In both cases, HLTF expression was assessed using immunohistochemistry (IHC) followed by microscopy computer-assisted quantification (percentage of immunopositive cells and staining intensity) and immunodetection on western blots (WB); subsequently, HLTF expression was correlated with the patient clinical outcome.…”

Section: Hltf Expression In Cancermentioning

confidence: 99%

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The helicase-like transcription factor (HLTF) in cancer: loss of function or oncomorphic conversion of a tumor suppressor?

Dhont

Mascaux

Belayew

2015

Cell. Mol. Life Sci.

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The Helicase-like Transcription Factor (HLTF) belongs to the SWI/SNF family of proteins involved in chromatin remodeling. In addition to its role in gene transcription, HLTF has been implicated in DNA repair, which suggests that this protein acts as a tumor suppressor. Accumulating evidence indicates that HLTF expression is altered in various cancers via two mechanisms: gene silencing through promoter hypermethylation or alternative mRNA splicing, which leads to the expression of truncated proteins that lack DNA repair domains. In either case, the alteration of HLTF expression in cancer has a poor prognosis. In this review, we gathered published clinical and molecular data on HLTF. Our purposes are (a) to address whether HLTF alterations could be considered as cancer drivers or passengers and (b) to determine whether its different functions (transcription or DNA repair) could be diverted in clonal selection during cancer progression.

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Section: Discussionmentioning

confidence: 86%

Section: Hltf Proteinsmentioning

confidence: 99%

Section: Hltf Expression In Cancermentioning

confidence: 99%

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The helicase-like transcription factor (HLTF) in cancer: loss of function or oncomorphic conversion of a tumor suppressor?

Dhont

Mascaux

Belayew

2015

Cell. Mol. Life Sci.

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“…The HLTF1∆A variant has lost the RING domain and the last 3 helicase domains. HLTF1∆B has only lost the last 3 helicase domains (Capouillez et al, 2009). Both proteins are predicted to have lost DNA repair activity.…”

Section: Descriptionmentioning

confidence: 99%

HLTF (helicase-like transcription factor)

Dimitrova¹,

Belayew²

2011

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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“…Taken together, our findings provide new mechanistic insights on genomic instability linked to helicase-like transcription factor deregulation, and strongly suggest a tumor suppressor function of the SWI/SNF protein in acute myeloid leukemia. 17,18 Unlike in solid tumors, the role of HLTF in hematological malignancies remains largely unclear. In this study, we sought to investigate potential HLTF deregulation and its clinicopathological and functional implications in acute myeloid leukemia (AML).…”

mentioning

confidence: 99%

Helicase-like transcription factor is a RUNX1 target whose downregulation promotes genomic instability and correlates with complex cytogenetic features in acute myeloid leukemia

et al. 2016

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H elicase-like transcription factor is a SWI/SNF chromatin remodeling factor involved in various biological processes. However, little is known about its role in hematopoiesis. In this study, we measured helicase-like transcription factor mRNA expression in the bone marrow of 204 adult patients with de novo acute myeloid leukemia. Patients were dichotomized into low and high expression groups at the median level for clinicopathological correlations. Helicaselike transcription factor levels were dramatically reduced in the low expression patient group compared to those in the normal controls (n=40) (P<0.0001). Low helicase-like transcription factor expression correlated positively with French-American-British M4/M5 subtypes (P<0.0001) and complex cytogenetic abnormalities (P=0.02 for ≥3 abnormalities; P=0.004 for ≥5 abnormalities) but negatively with CEBPA double mutations (P=0.012). Also, low expression correlated with poorer overall (P=0.005) and event-free (P=0.006) survival in the intermediate-risk cytogenetic subgroup. Consistent with the more aggressive disease associated with low expression, helicase-like transcription factor knockdown in leukemic cells promoted proliferation and chromosomal instability that was accompanied by downregulation of mitotic regulators and impaired DNA damage response. The significance of helicase-like transcription factor in genome maintenance was further indicated by its markedly elevated expression in normal human CD34 + hematopoietic stem cells. We further demonstrated that helicase-like transcription factor was a RUNX1 target and transcriptionally repressed by RUNX1-ETO and site-specific DNA methylation through a duplicated RUNX1 binding site in its promoter. Taken together, our findings provide new mechanistic insights on genomic instability linked to helicase-like transcription factor deregulation, and strongly suggest a tumor suppressor function of the SWI/SNF protein in acute myeloid leukemia.

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The helicase‐like transcription factor is a strong predictor of recurrence in hypopharyngeal but not in laryngeal squamous cell carcinomas

Cited by 20 publications

References 29 publications

The helicase-like transcription factor (HLTF) in cancer: loss of function or oncomorphic conversion of a tumor suppressor?

The helicase-like transcription factor (HLTF) in cancer: loss of function or oncomorphic conversion of a tumor suppressor?

HLTF (helicase-like transcription factor)

Helicase-like transcription factor is a RUNX1 target whose downregulation promotes genomic instability and correlates with complex cytogenetic features in acute myeloid leukemia

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