Functional interactions between tetraspanin CD9 and cell adhesion molecules

Research summary:

The tetraspanin CD9 displays a high ability to interact with other surface proteins in several types of cells. Through these interactions, CD9 regulates key cellular processes such as adhesion, migration, invasion and proliferation.

ADAM17/TACE is protease responsible for ectodomain "shedding" of a large number of cell surface proteins that are critically involved in development, growth, adhesion, differentiation, and migration of leukocytes and tumor cells. ADAM-17/TACE is particularly important in the regulation of cell adhesion through the shedding of different adhesion molecules that either belong to the immunoglobulin superfamily (ICAM-1, VCAM-1, NCAM, L1CAM AND ALCAM) or to other families of adhesion receptors (CD44 and L-selectin).

ALCAM/CD166 is a transmembrane glycoprotein of 110 kDa with five Ig-type domains in its extracellular region, a single transmembrane region and a short intracytoplasmic tail. ALCAM mediates cell adhesion through homophilic (ALCAM-ALCAM) as well as heterophilic (ALCAM-CD6) interactions, and has been implicated in the invasive growth and metastasis of different types of tumors (melanomas and breast, prostate, ovary and colorectal carcinomas). ALCAM can be cleaved at its juxtamembrane extracellular region by ADAM-17/TACE, causing the release of a 96 kDa soluble form (sALCAM). The circulating levels of sALCAM are elevated in patients of different types of cancers, which suggests the implication of this molecule in the motility and invasion of malignant cells.

Our recent results have demonstrated that CD9 is capable to regulate the adhesion of tumoral cells through a dual mechanism. On the one hand, this tetraspanin induces the aggregation of different adhesion molecules though specific interactions inducing their recruitment into cell surface microdomains termed TEMs (Tetraspanin-Enriched Microdomains), which in turn induces changes in the avidity of these molecules for their ligands. Additionally, CD9 negatively regulates the proteolytic activity of ADAM-17/TACE and through this effect is able to control the balance between the transmembrane and soluble forms (and hence the activity) of different proteins involved in cell adhesion and inflammation, including TNF-α, ICAM-1 and ALCAM.


Confocal microscopy analysis of the co-localization between the adhesion molecule ALCAM/CD166 and the tetraspanin CD9 in Jurkat T cells, CD9-transfected Raji B cells and BLM melanoma cells. Partial co-localization of these molecules is observed on the plasma membrane of the three cell types. Interestingly, the areas of co-localization between CD9 and ALCAM on lymphoid cells are distributed following a patched pattern while on the adherent BLM melanoma cells co-localization is particularly enriched in cell-cell contacts.


* For external calls please dial 34 91196 followed by the extension number
Last nameNameLaboratoryExt.*e-mailProfessional category
Cabañas GutiérrezCarlos1254513ccabanas(at)cbm.csic.esE. Investigadores Científicos de Organismos Públicos
Cardeñes PérezBeatriz1254531bcardenes(at)cbm.csic.esTitulado Sup. Actividades Tecn. y Prof.GP1 50%
Clares PedreroIrene1254513irene.clares(at)cbm.csic.esGJ-AI y TL_Titulado Sup. Actividades Técn. y Prof.GP1
Fernández RodríguezAna Mª663930632Estudiante TFM
Melones DelgadoAlejandro1254513Estudiante TFG

Relevant publications:

  • Gutiérrez-López, M.D., Gilsanz, A., Yánez-Mó, M., Ovalle, S., Lafuente, M.E., Domínguez, C., Monk, P.N., González-Alvaro, I., Sánchez-Madrid, F., and Cabañas, C. (2011). The sheddase activity of ADAM17/TACE is regulated by the tetraspanin CD9. Cellular and Molecular Life Sciences 68:3275-3292.
  • Yánez-Mó, M., Sánchez-Madrid, F. and Cabañas C. (2011). Membrane proteases and tetraspanins. Biochemical Society Transactions 39:541-546.
  • Hernández-Varas, P., Coló, G.P., Bartolomé, R.A., Paterson, A., Medraño-Fernández, I., Cabañas, C., Sánchez-Mateos, P., Lafuente, E.M., Boussiotis, V.A., Strömblad, S. and Teixidó, J. (2011). Rap1-GTP-interacting adaptor molecule (RIAM) protein controls invasion and growth of melanoma cells. Journal of Biological Chemistry 286:18492-18504.
  • Yáñez-Mó, M., Gutiérrez-López, M.D., and Cabañas, C. (2011). Functional interplay between tetraspanins and proteases. Cellular and Molecular Life Sciences 68:3323-35.
  • Rossi, E., Langa, C., Gilsanz, A., Blanco, F.J., Ayllón, J., Villar, E., Botella, L.M., Cabañas, C., Shaw, M., and Bernabeu, C. (2012). Characterization of chicken endoglin, a member of the zona pellucida family of proteins, and its tissue expression. Gene 491:31-9.

Doctoral theses:

  • Iria Medraño Fernández (2012). Papel de la proteína adaptadora RIAM en la fagocitosis mediada por complemento. Universidad Complutense de Madrid. Directores: Dra. Mª Esther Lafuente y Dr. Carlos Cabañas.
  • Álvaro Gilsanz Cáceres (2012). La tetraspanina CD9 regula la función de la metaloproteasa ADAM17/TACE y de su sustrato ALCAM. Universidad Complutense de Madrid. Director: Dr. Carlos Cabañas.

NOTE! This site uses cookies and similar technologies.

If you not change browser settings, you agree to it. Learn more

I understand


What are cookies?

A cookie is a file that is downloaded to your computer when you access certain web pages. Cookies allow a web page, among other things, to store and retrieve information about the browsing habits of a user or their equipment and, depending on the information they contain and the way they use their equipment, they can be used to recognize the user.

Types of cookies

Classification of cookies is made according to a series of categories. However, it is necessary to take into account that the same cookie can be included in more than one category.

  1. Cookies according to the entity that manages them

    Depending on the entity that manages the computer or domain from which the cookies are sent and treat the data obtained, we can distinguish:

    • Own cookies: those that are sent to the user's terminal equipment from a computer or domain managed by the editor itself and from which the service requested by the user is provided.
    • Third party cookies: those that are sent to the user's terminal equipment from a computer or domain that is not managed by the publisher, but by another entity that processes the data obtained through the cookies. When cookies are installed from a computer or domain managed by the publisher itself, but the information collected through them is managed by a third party, they cannot be considered as own cookies.

  2. Cookies according to the period of time they remain activated

    Depending on the length of time that they remain activated in the terminal equipment, we can distinguish:

    • Session cookies: type of cookies designed to collect and store data while the user accesses a web page. They are usually used to store information that only is kept to provide the service requested by the user on a single occasion (e.g. a list of products purchased).
    • Persistent cookies: type of cookies in which the data is still stored in the terminal and can be accessed and processed during a period defined by the person responsible for the cookie, which can range from a few minutes to several years.

  3. Cookies according to their purpose

    Depending on the purpose for which the data obtained through cookies are processed, we can distinguish between:

    • Technical cookies: those that allow the user to navigate through a web page, platform or application and the use of different options or services that exist in it, such as controlling traffic and data communication, identifying the session, access to restricted access parts, remember the elements that make up an order, perform the purchase process of an order, make a registration or participation in an event, use security elements during navigation, store content for the broadcast videos or sound or share content through social networks.
    • Personalization cookies: those that allow the user to access the service with some predefined general characteristics based on a series of criteria in the user's terminal, such as the language, the type of browser through which the user accesses the service, the regional configuration from where you access the service, etc.
    • Analytical cookies: those that allow the person responsible for them to monitor and analyse the behaviour of the users of the websites to which they are linked. The information collected through this type of cookies is used in the measurement of the activity of the websites, applications or platforms, and for the elaboration of navigation profiles of the users of said sites, applications and platforms, in order to introduce improvements in the analysis of the data of use made by the users of the service.

Cookies used on our website

The CBMSO website uses Google Analytics. Google Analytics is a simple and easy to use tool that helps website owners to measure how users interact with the content of the site. You can consult more information about the cookies used by Google Analitycs in this link.

Acceptance of the Cookies Policy

The CBMSO assumes that you accept the use of cookies if you continue browsing, considering that it is a conscious and positive action from which the user's consent is inferred. In this regard, you are previously informed that such behaviour will be interpreted that you accept the installation and use of cookies.

Knowing this information, it is possible to carry out the following actions:

  • Accept cookies: if the user presses the acceptance button, this warning will not be displayed again when accessing any page of the portal.
  • Review the cookies policy: the user can access to this page in which the use of cookies is detailed, as well as links to modify the browser settings.

How to modify the configuration of cookies

Using your browser you can restrict, block or delete cookies from any web page. In each browser the process is different, here we show you links on this particular of the most used browsers: