Редактирование: HOPX

Homeodomain-only protein (Lung cancer-associated Y protein) (Not expressed in choriocarcinoma protein 1) (Odd homeobox protein 1) [HOD] [HOP] [LAGY] [NECC1] [OB1]

==Publications==

{{medline-entry
|title=Combinations of differentiation markers distinguish subpopulations of alveolar epithelial cells in adult lung.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26545903
|abstract=Distal lung epithelium is maintained by proliferation of alveolar type II (AT2) cells and, for some daughter AT2 cells, transdifferentiation into alveolar type I (AT1) cells. We investigated if subpopulations of alveolar epithelial cells (AEC) exist that represent various stages in transdifferentiation from AT2 to AT1 cell phenotypes in normal adult lung and if they can be identified using combinations of cell-specific markers. Immunofluorescence microscopy showed that, in distal rat and mouse lungs, ∼ 20-30% of NKX2.1( ) (or thyroid transcription factor 1( )) cells did not colocalize with pro-surfactant protein C (pro-SP-C), a highly specific AT2 cell marker. In distal rat lung, NKX2.1( ) cells coexpressed either pro-SP-C or the AT1 cell marker homeodomain only protein x ([[HOPX]]). Not all [[HOPX]]( ) cells colocalize with the AT1 cell marker aquaporin 5 ([[AQP5]]), and some [[AQP5]]( ) cells were NKX2.1( ). [[HOPX]] was expressed earlier than [[AQP5]] during transdifferentiation in rat AEC primary culture, with robust expression of both by day 7. We speculate that NKX2.1 and pro-SP-C colocalize in AT2 cells, NKX2.1 and [[HOPX]] or [[AQP5]] colocalize in intermediate or transitional cells, and [[HOPX]] and [[AQP5]] are expressed without NKX2.1 in AT1 cells. These findings suggest marked heterogeneity among cells previously identified as exclusively AT1 or AT2 cells, implying the presence of subpopulations of intermediate or transitional AEC in normal adult lung.
|mesh-terms=* Aging
* Alveolar Epithelial Cells
* Animals
* Antigens, Differentiation
* Cell Differentiation
* Cell Transdifferentiation
* Cells, Cultured
* Epithelial Cells
* Mice
* Pulmonary Alveoli
* Rats
|keywords=* NKX2.1
* alveolar epithelial type I cell
* alveolar epithelial type II cell
* aquaporin-5
* homeodomain only protein x
* intermediate cells
* transdifferentiation
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4719049
}}
{{medline-entry
|title=[[HOPX]] is methylated and exerts tumour-suppressive function through Ras-induced senescence in human lung cancer.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/25345926
|abstract=[[HOPX]] acts as a tumour suppressor in various cancers. However, the regulation of [[HOPX]] in human lung cancer as well as the mechanism underlying its tumour-suppressive function has not yet been well elucidated. Here we investigated the epigenetic regulation and molecular mechanism by which [[HOPX]] exerts growth inhibitory effects. We found that [[HOPX]] was down-regulated in 12 out of 13 lung cancer cell lines and in 69 out of 120 primary lung tumours at mRNA and protein levels. Patients with lung adenocarcinoma (ADC) exhibited significantly more positive staining of [[HOPX]] protein compared with lung squamous cell carcinoma (SCC) (p =0.036). Again in ADC, patients with higher [[HOPX]] expression had a significantly longer disease-free survival (p =0.001). Methylation analysis showed that down-regulation of [[HOPX]] was associated with DNA methylation (p =0.011). To analyse the function of [[HOPX]] in lung cancer cells, stable transfection with an expression vector of [[HOPX]] was performed. It turned out that [[HOPX]] inhibited tumour cell proliferation rate, migration, and invasion, and, more interestingly, forced expression of [[HOPX]] enhanced cellular senescence via activation of oncogenic Ras and the downstream MAPK pathway, which in turn led to decreased MDM2 and increased p21. On the contrary, knockdown of [[HOPX]] by siRNA resulted in reduced Ras activity, inactivation of the MAPK pathway, and decreased p21 levels, accompanied by reduced cellular senescence. Additionally, the [[HOPX]]-induced senescence pathway was also active in human bronchial epithelial cells. Taken together, our data suggest that down-regulation of [[HOPX]] was related to DNA methylation and that [[HOPX]] exerts tumour-suppressive activity by oncogenic Ras-induced cellular senescence in lung cancer cells.
|mesh-terms=* Adenocarcinoma
* Carcinoma, Non-Small-Cell Lung
* Carcinoma, Squamous Cell
* Cell Line, Tumor
* Cell Movement
* Cell Proliferation
* Cells, Cultured
* Cellular Senescence
* DNA Methylation
* Down-Regulation
* Gene Expression Regulation, Neoplastic
* Homeodomain Proteins
* Humans
* Lung Neoplasms
* Signal Transduction
* Small Cell Lung Carcinoma
* Tumor Suppressor Proteins
* ras Proteins
|keywords=* HOPX
* Ras-induced senescence
* lung cancer
* methylation
|full-text-url=https://sci-hub.do/10.1002/path.4469
}}