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.

HOXB7 overexpression in lung cancer is a hallmark of acquired stem-like phenotype / S. Monterisi, P.L. Riso, K. Russo, G. Bertalot, M. Vecchi, G. Testa, P.P. Di Fiore, F. Bianchi. - In: ONCOGENE. - ISSN 0950-9232. - (2018 Mar 26), pp. 1-14. [Epub ahead of print]

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

Riso, Pietro Lo;Testa, Giuseppe;Di Fiore, Pier Paolo;
2018-03-26

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.
Molecular Biology; Genetics; Cancer Research
Settore MED/04 - Patologia Generale
Settore BIO/11 - Biologia Molecolare
26-mar-2018
ONCOGENE
Article (author)
File in questo prodotto:
File Dimensione Formato  
02 Monterisi et al_Oncogene.pdf

non disponibili

Descrizione: Full Article
2.31 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/569598
Citazioni
  • ???jsp.display-item.citation.pmc??? 13
  • Scopus 23
  • ???jsp.display-item.citation.isi??? 22
social impact