HOX proteins: from molecular interactions to cancer and development

Embryonic development, cell behavior, appearance of cancer are genetically controlled phenomena. Hox genes code for proteins whose main known roles are to control expression of other genes, therefore called target genes. HOX proteins thereby act as master regulators of lots of processes in animals from cell division to cell differentiation, cell migration or cell-to-cell communication. During animal development HOX proteins critically contribute to the shaping of the embryo. Their activities confer their fate to several embryonic structures that ultimately give rise to vertebrae, limbs, organ parts or functional centers of the nervous system.

While the functions of Hox genes have been intensely studied since their discovery in the late 70s, the mode of action of HOX proteins remains surprisingly scarcely characterized. The various target genes they are presumed to control in specific cell contexts remain largely unknown. The various proteins they are expected to interact with to fulfill their functions also remain to be identified.

The research objectives of our group is to characterize the molecular mode of action of HOX proteins and to relate this with the cellular activities and developmental processes they are involved in.

The HOXA2 interactome. HOXA2 appears as a red node. The color of the nodes is indicative of their centroid value (green, low; orange, high; network generated with Cytoscape; by Isabelle Bergiers).

HOX proteins and the control of gene expression
HOX protein function is to control the activity of so-called target genes. Understanding the mode of action of HOX proteins in this context will consist in deciphering how do HOX proteins recognize genes, i.e. how they bind DNA in the vicinity of genes and how this eventually results in gene activity.

HOX proteins and cell behavior
We identified that HOX proteins could endorse functions which are not related to the control of gene expression. We recently highlighted that HOX proteins can interact with other proteins involved in processes like cell-to-cell communication, cell proliferation, cell adhesion etc. An important part of our research is to shed light on these unexpected activities of HOX proteins. One particular issue relates to cancer: some Hox genes have indeed been identified as promoting the onset and the progression of several kinds of cancers.

In situ hybridization: The RCHY1 gene coding for a HOXA2 interactor is expressed in the neuro-epithelium of the hindbrain (by Laure Bridoux; see Bridoux et al., 2015).

HOX proteins and development
The genes and cellular processes under the control of HOX proteins are functionally interconnected in developing and living animals. HOX proteins govern the development of organs or functional units of organs. We also pursue the aim of relating what we can learn from the mode of action of HOX proteins to these biological processes they are involved in.