Hoxb8, a member of the Hox family, is involved in crucial biological processes. It is an oncoprotein that can enforce self-renewal of factor-dependent myeloid progenitors [1]. Hoxb8 is also related to pathways such as the MAPK/ERK signaling pathway, where it acts as a tumor suppressor, counteracting ERK-induced neoplasia by reverting the oncogenic transcriptome [5]. Additionally, it activates the STAT3 pathway in several cancers, playing roles in tumor-related processes [4,6,7].

In murine studies, a sub-population of microglia, known as Hoxb8 microglia, is derived from the Hoxb8 lineage during the second wave of yolk sac hematopoiesis. Dysfunctional Hoxb8 microglia cause chronic anxiety and trichotillomania-like behavior in mice [2]. The Hoxb8 cell lineage reporter has been used to define the ontogeny of hematopoietic cells, showing that Hoxb8 progenitors and microglia require Myb function for propagation and maturation [2]. Conditionally HoxB8-immortalized mouse hematopoietic progenitors are suitable for in vitro differentiation of myeloid cells like neutrophils, which respond to FcγR and integrin stimulation similar to primary neutrophils [3].

In summary, Hoxb8 is essential in hematopoiesis, especially in the development of certain microglia and myeloid cells. In disease areas, it is involved in cancer-related processes such as cell proliferation, metastasis, and drug resistance through activation of pathways like STAT3, as demonstrated by studies in mouse models and cell lines [2,3,4,6,7].

References:

1. Wang, Gang G, Calvo, Katherine R, Pasillas, Martina P, Häcker, Hans, Kamps, Mark P. . Quantitative production of macrophages or neutrophils ex vivo using conditional Hoxb8. In Nature methods, 3, 287-93. doi:. https://pubmed.ncbi.nlm.nih.gov/16554834/

2. Van Deren, Donn A, De, Shrutokirti, Xu, Ben, Zhang, Shuhua, Capecchi, Mario R. 2022. Defining the Hoxb8 cell lineage during murine definitive hematopoiesis. In Development (Cambridge, England), 149, . doi:10.1242/dev.200200. https://pubmed.ncbi.nlm.nih.gov/35452096/

3. Chu, Julia Y, McCormick, Barry, Mazelyte, Greta, Michael, Melina, Vermeren, Sonja. 2018. HoxB8 neutrophils replicate Fcγ receptor and integrin-induced neutrophil signaling and functions. In Journal of leukocyte biology, 105, 93-100. doi:10.1002/JLB.1AB0618-232R. https://pubmed.ncbi.nlm.nih.gov/30211955/

4. Wang, Tingting, Lin, Feiyan, Sun, Xuecheng, Lu, Fengying, Li, Shaotang. 2019. HOXB8 enhances the proliferation and metastasis of colorectal cancer cells by promoting EMT via STAT3 activation. In Cancer cell international, 19, 3. doi:10.1186/s12935-018-0717-6. https://pubmed.ncbi.nlm.nih.gov/30622439/

5. Wilmerding, Axelle, Bouteille, Lauranne, Rinaldi, Lucrezia, Graba, Yacine, Delfini, Marie-Claire. 2021. HOXB8 Counteracts MAPK/ERK Oncogenic Signaling in a Chicken Embryo Model of Neoplasia. In International journal of molecular sciences, 22, . doi:10.3390/ijms22168911. https://pubmed.ncbi.nlm.nih.gov/34445617/

6. Liang, Yunan, Lin, Han, Jiang, Zongsheng, Cui, Ri, Li, Shaotang. 2024. HOXB8 mediates resistance to cetuximab in colorectal cancer cells through activation of the STAT3 pathway. In Discover oncology, 15, 603. doi:10.1007/s12672-024-01440-z. https://pubmed.ncbi.nlm.nih.gov/39472327/

7. Liu, Lidan, Wang, Lifei, Li, Xiujuan. 2022. The roles of HOXB8 through activating Wnt/β-catenin and STAT3 signaling pathways in the growth, migration and invasion of ovarian cancer cells. In Cytotechnology, 74, 77-87. doi:10.1007/s10616-021-00508-w. https://pubmed.ncbi.nlm.nih.gov/35185287/