HOXB7 overexpression in lung cancer is a hallmark of acquired stem-like phenotype

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Abstract

HOXB7 is a homeodomain (HOX) transcription factor involved in regional body patterning of invertebrates and vertebrates. We previously identified HOXB7 within a ten-gene prognostic signature for lung adenocarcinoma, where increased expression of HOXB7 was associated with poor prognosis. This raises the question of how HOXB7 overexpression can influence the metastatic behavior of lung adenocarcinoma. Here, we analyzed publicly available microarray and RNA-seq lung cancer expression datasets and found that HOXB7-overexpressing tumors are enriched in gene signatures characterizing adult and embryonic stem cells (SC), and induced pluripotent stem cells (iPSC). Experimentally, we found that HOXB7 upregulates several canonical SC/iPSC markers and sustains the expansion of a subpopulation of cells with SC characteristics, through modulation of LIN28B, an emerging cancer gene and pluripotency factor, which we discovered to be a direct target of HOXB7. We validated this new circuit by showing that HOXB7 enhances reprogramming to iPSC with comparable efficiency to LIN28B or its target c-MYC, which is a canonical reprogramming factor.

Original languageEnglish
Pages (from-to)3575-3588
Number of pages14
JournalOncogene
Volume37
Issue number26
DOIs
Publication statusPublished - Jun 2018

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Induced Pluripotent Stem Cells
Lung Neoplasms
Phenotype
Stem Cells
Body Patterning
Adult Stem Cells
Neoplasm Genes
Invertebrates
Embryonic Stem Cells
Genes
Vertebrates
Transcription Factors
Up-Regulation
RNA
Neoplasms
Adenocarcinoma of lung

Cite this

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title = "HOXB7 overexpression in lung cancer is a hallmark of acquired stem-like phenotype",
abstract = "HOXB7 is a homeodomain (HOX) transcription factor involved in regional body patterning of invertebrates and vertebrates. We previously identified HOXB7 within a ten-gene prognostic signature for lung adenocarcinoma, where increased expression of HOXB7 was associated with poor prognosis. This raises the question of how HOXB7 overexpression can influence the metastatic behavior of lung adenocarcinoma. Here, we analyzed publicly available microarray and RNA-seq lung cancer expression datasets and found that HOXB7-overexpressing tumors are enriched in gene signatures characterizing adult and embryonic stem cells (SC), and induced pluripotent stem cells (iPSC). Experimentally, we found that HOXB7 upregulates several canonical SC/iPSC markers and sustains the expansion of a subpopulation of cells with SC characteristics, through modulation of LIN28B, an emerging cancer gene and pluripotency factor, which we discovered to be a direct target of HOXB7. We validated this new circuit by showing that HOXB7 enhances reprogramming to iPSC with comparable efficiency to LIN28B or its target c-MYC, which is a canonical reprogramming factor.",
author = "Simona Monterisi and {Lo Riso}, Pietro and Karin Russo and Giovanni Bertalot and Manuela Vecchi and Giuseppe Testa and {Di Fiore}, {Pier Paolo} and Fabrizio Bianchi",
year = "2018",
month = "6",
doi = "10.1038/s41388-018-0229-9",
language = "English",
volume = "37",
pages = "3575--3588",
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TY - JOUR

T1 - HOXB7 overexpression in lung cancer is a hallmark of acquired stem-like phenotype

AU - Monterisi, Simona

AU - Lo Riso, Pietro

AU - Russo, Karin

AU - Bertalot, Giovanni

AU - Vecchi, Manuela

AU - Testa, Giuseppe

AU - Di Fiore, Pier Paolo

AU - Bianchi, Fabrizio

PY - 2018/6

Y1 - 2018/6

N2 - HOXB7 is a homeodomain (HOX) transcription factor involved in regional body patterning of invertebrates and vertebrates. We previously identified HOXB7 within a ten-gene prognostic signature for lung adenocarcinoma, where increased expression of HOXB7 was associated with poor prognosis. This raises the question of how HOXB7 overexpression can influence the metastatic behavior of lung adenocarcinoma. Here, we analyzed publicly available microarray and RNA-seq lung cancer expression datasets and found that HOXB7-overexpressing tumors are enriched in gene signatures characterizing adult and embryonic stem cells (SC), and induced pluripotent stem cells (iPSC). Experimentally, we found that HOXB7 upregulates several canonical SC/iPSC markers and sustains the expansion of a subpopulation of cells with SC characteristics, through modulation of LIN28B, an emerging cancer gene and pluripotency factor, which we discovered to be a direct target of HOXB7. We validated this new circuit by showing that HOXB7 enhances reprogramming to iPSC with comparable efficiency to LIN28B or its target c-MYC, which is a canonical reprogramming factor.

AB - HOXB7 is a homeodomain (HOX) transcription factor involved in regional body patterning of invertebrates and vertebrates. We previously identified HOXB7 within a ten-gene prognostic signature for lung adenocarcinoma, where increased expression of HOXB7 was associated with poor prognosis. This raises the question of how HOXB7 overexpression can influence the metastatic behavior of lung adenocarcinoma. Here, we analyzed publicly available microarray and RNA-seq lung cancer expression datasets and found that HOXB7-overexpressing tumors are enriched in gene signatures characterizing adult and embryonic stem cells (SC), and induced pluripotent stem cells (iPSC). Experimentally, we found that HOXB7 upregulates several canonical SC/iPSC markers and sustains the expansion of a subpopulation of cells with SC characteristics, through modulation of LIN28B, an emerging cancer gene and pluripotency factor, which we discovered to be a direct target of HOXB7. We validated this new circuit by showing that HOXB7 enhances reprogramming to iPSC with comparable efficiency to LIN28B or its target c-MYC, which is a canonical reprogramming factor.

U2 - 10.1038/s41388-018-0229-9

DO - 10.1038/s41388-018-0229-9

M3 - Article

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VL - 37

SP - 3575

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JO - Oncogene

JF - Oncogene

SN - 0950-9232

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