1. HOXB7 overexpression in lung cancer is a hallmark of acquired stem-like phenotype
- Author
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Manuela Vecchi, Giovanni Bertalot, Fabrizio Bianchi, Giuseppe Testa, Pietro Lo Riso, Simona Monterisi, Karin Russo, and Pier Paolo Di Fiore
- Subjects
0301 basic medicine ,Cancer Research ,Lung Neoplasms ,Induced Pluripotent Stem Cells ,Adenocarcinoma of Lung ,Biology ,Proto-Oncogene Proteins c-myc ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Cell Line, Tumor ,Genetics ,medicine ,Humans ,RNA, Small Interfering ,Lung cancer ,Induced pluripotent stem cell ,Molecular Biology ,Embryonic Stem Cells ,Cell Proliferation ,Homeodomain Proteins ,Regulation of gene expression ,Gene Expression Profiling ,RNA-Binding Proteins ,Cancer ,medicine.disease ,Embryonic stem cell ,Gene Expression Regulation, Neoplastic ,Gene expression profiling ,HEK293 Cells ,030104 developmental biology ,030220 oncology & carcinogenesis ,Neoplastic Stem Cells ,Cancer research ,Adenocarcinoma ,RNA Interference ,Reprogramming - 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.
- Published
- 2018