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Team Chloé FERAL


Basic Research Team "Epithelial homeostasis and tumorigenesis"

Dr Chloé FERAL, DR2 INSERM, Team Leader

Figure 1. CD98 heterodimer : the heavy subunit (pink)
and the light subunit (blue) are linked by a disulfide bridge (yellow)
with conserved cysteine residues
(from Palacin M. et al. Physiology, Vol. 20, No. 2, 112-124, April 2005)


The cells that compose the epithelium are constantly renewed. To maintain homeostasis in an adult tissue, cell proliferation must be tightly regulated, yet how this is controlled is not fully understood. When this balance is lost and too many cells accumulate, epithelial cancers (or carcinomas) arise. In particular, squamous cell carcinoma (SCC) is the second most common type of skin cancer and its incidence increases with age. Our lab is investigating the role of CD98hc, a dual function transmembrane protein, in epidermal tumor formation.

Epithelial cells rest on a basal membrane composed of highly organized network of extracellular matrix (ECM) proteins. Tumor formation greatly depend on cell adhesion, migration and proliferation which are regulated by both ECM and integrins, a family of cell-surface receptors that interact with ECM proteins. Integrins function as bi-directional signaling molecules.

CD98, originally identified as the 4F2 antigen, is highly expressed in keratinocytes. Its expression also correlates with increased morphological grade and worsened prognosis of tumors, independent of their tissue of origin. CD98 is a heterodimer of a common heavy chain (CD98hc, SLC3A2), and one of several light chains (CD98lc) that each has multiple membrane spanning domains. CD98hc has two main functions: amino acid transporter (via its interaction with a CD98lc) and integrin signaling modulator (via its interaction with β integrins). Its knock-out is embryonic lethal.

The CD98hc-integrin complex plays a crucial role in cell behavior that depends on cell proliferation, migration and survival. Besides, the CD98 heterodimer (heavy chain and light chain) contributes to efficient amino-acid transport, which is vital for cell survival and proliferation.

Our work aims at determining how CD98 interactions contribute to epidermal homeostasis and tumorigenesis.

Figure 2. CD98hc Expression in the basal layer of human epidermis (green CD98hc, blue DAPI)


Research Project

Research Project

Previously generated CD98hcfl/fl murine line will be used to determine the role of CD98hc in epidermal homeostasis and skin cancer in vivo. Furthermore, we will decipher the cellular and molecular events resulting from CD98hc deletion in vitro.

The proposed work will revolve around 3 main axes :

1) Determine the role of CD98hc in skin homeostasis and tumorigenesis in vivo

2) Analyze in vitro CD98hc implication in regulating integrin function and amino-acid transport in murine keratinocytes

3) Investigate the molecular mechanisms involved downstream of CD98hc and assess the roles of the different CD98hc domains on its biological activities.

Press Articles

Regional Newspaper Nice-Matin, October 12th, 2013

"Skin aging, soon under control ?"

Research Team


Research Team (2016)

FERAL Chloé, DR2 INSERM, Chef d'Equipe
Tel : +33 (0)4 93 37 76 18
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Tel : +33 (0)4 93 37 70 93, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it

CAILLETEAU Laurence, AI Inserm
Tel : +33 (0)4 93 37 70 32, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it

De GARAY-HERRERA Tomas, Etudiant en Thèse

Tel : +33 (0)4 93 37 70 85, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Tel : +33 (0)4 93 37 70 93, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it

TISSOT Floriane, Etudiante PhD

Tel : +33 (0)4 93 37 70 85, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it

TOSELLO Lionel, CDD Ingénieur INSERM

Tel : +33 (0)4 93 37 70 85, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it

Lab : +33 (0)4 93 37 70 85




Feral CC, Tissot FS, Tosello L, Fakhry N, Sebag F, Pacak K, Taïeb D.

18F-fluorodihydroxyphenylalanine PET/CT in pheochromocytoma and paraganglioma: relation to genotype and amino acid transport system L.

Eur J Nucl Med Mol Imaging. 2016, Nov 29.

Tissot FS, Boulter E, Estrach S, Féral CC.

The body's tailored suit: Skin as a mechanical interface.

Eur J Cell Biol. 2016 Nov;95(11):475-482.

De la Ballina LR, Cano-Crespo S, González-Muñoz E, Bial S, Estrach S, Cailleteau L, Tissot F, Daniel H, Zorzano A, Ginsberg MH, Palacín M, Féral CC.

Amino Acid Transport Associated to Cluster of Differentiation 98 Heavy Chain (CD98hc) Is at the Cross-road of Oxidative Stress and Amino Acid Availability.

J Biol Chem. 2016 Apr 29;291(18):9700-11.


Albrengues J, Bertero T, Grasset E, Bonan S, Maiel M, Bourget I, Philippe C, Herraiz Serrano C,

Benamar S, Croce O, Sanz-Moreno V, Meneguzzi G, Feral CC, Cristofari G, Gaggioli C.

Epigenetic switch drives the conversion of fibroblasts into proinvasive cancer-associated fibroblasts.

Nat Commun., 2015, Dec15;6:10204.

Brahimi-Horn MC, Giuliano S, Saland E, Lacas-Gervais S, Sheiko T, Pelletier J, Bourget I,

Bost F, Féral C, Boulter E, Tauc M, Ivan M, Garmy-Susini B, Popa A, Mari B, Sarry JE,

Craigen WJ, Pouysségur J, Mazure NM.

Knockout of Vdac1 activates hypoxia-inducible factor through reactive oxygen species

generation and induces tumor growth by promoting metabolic reprogramming and inflammation.

Cancer Metab., 2015, Aug26;3:8.

Keriel A, Botella E, Estrach S, Bragagnolo G, Vergunst AC, Feral CC, O'Callaghan D.

Brucella Intracellular Life Relies on the Transmembrane Protein CD98 Heavy Chain.

J Infect Dis., 2015, Jun1;211(11):1769-78.


Estrach S, Lee SA, Boulter E, Pisano S, Errante A, Tissot FS, Cailleteau L, Pons C,

Ginsberg MH, Féral CC.

CD98hc (SLC3A2) loss protects against ras-driven tumorigenesis by modulating

integrin-mediated mechanotransduction.

Cancer Res., 2014, Dec1;74(23):6878-89.

Albrengues J, Bourget I, Pons C, Butet V, Hofman P, Tartare-Deckert S, Féral CC,

Meneguzzi G, Gaggioli C.

LIF mediates proinvasive activation of stromal fibroblasts in cancer.

Cell. Rep., 2014, Jun 12;7(5):1664-78.


Boulter E, Estrach S, Errante A, Pons C, Cailleteau L, Tissot F, Meneguzzi G, Féral CC.

CD98hc (SLC3A2) regulation of skin homeostasis wanes with age.

J. Exp. Med., 2013, Jan 14;210(1):173-90.


Mothe-Satney I, Filloux C, Amghar H, Pons C, Bourlier V, Galitzky J, Grimaldi PA, Féral CC,

Bouloumié A, Van Obberghen E, Neels JG.

Adipocytes secrete leukotrienes: contribution to obesity-associated inflammation and insulin

resistance in mice.

Diabetes, 2012, Sep;61(9):2311-9.

Boulter E, Estrach S, Garcia-Mata R, Féral CC.

Off the beaten paths : alternative and crosstalk regulation of Rho GTPases.

FASEB J., 2012, Feb;26(2):469-79.

Bulus N, Feral C, Pozzi A, Zent R.

CD98 increases renal epithelial cell proliferation by activating MAPKs.

PLoS One, 2012;7(6):e40026.


Sanz-Moreno V, Gaggioli C, Yeo M, Albrengues J, Wallberg F, Viros A, Hooper S, Mitter R,

Féral CC, Cook M, Larkin J, Marais R, Meneguzzi G, Sahai E, Marshall CJ.

ROCK and JAK1 signaling cooperate to control actomyosin contractility in tumor

cells and stroma.

Cancer Cell., 2011, Aug 16;20(2):229-45.


Garmy-Susini B, Avraamides CJ, Schmid MC, Foubert P, Ellies LG, Barnes L, Feral C,

Papayannopoulou T, Lowy A, Blair SL, Cheresh D, Ginsberg M, Varner JA.

Integrin alpha4beta1 signaling is required for lymphangiogenesis and tumor metastasis.

Cancer Res. 2010 Apr 15;70(8):3042-51.


Fogelstrand P, Féral CC, Zargham R, Ginsberg MH.

Dependence of proliferative vascular smooth muscle cells on CD98hc (4F2hc, SLC3A2). 

J Exp Med. 2009, Oct 26;206(11):2397-406.

Cantor J, Browne CD, Ruppert R, Féral CC, Fässler R, Rickert RC, Ginsberg MH.

CD98hc facilitates B cell proliferation and adaptive humoral immunity. 

Nat Immunol., 2009, Apr;10(4):412-9.


Helsten TL, Bunch TA, Kato H, Yamanouchi J, Choi SH, Jannuzi AL, Féral CC, Ginsberg MH,

Brower DL, Shattil SJ.

Differences in regulation of Drosophila and vertebrate integrin affinity by talin. 

Mol Biol Cell., 2008, Aug;19(8):3589-98.

Féral CC, Neels JG, Kummer C, Slepak M, Olefsky JM, Ginsberg MH.

Blockade of alpha4 integrin signaling ameliorates the metabolic consequences of

high-fat diet-induced obesity. 

Diabetes. 2008 Jul;57(7):1842-51.


Prager GW, Féral CC, Kim C, Han J, Ginsberg MH.

CD98hc (SLC3A2) interaction with the integrin beta subunit cytoplasmic domain

mediates adhesive signaling. 

J Biol Chem. 2007 Aug 17;282(33):24477-84.

Féral CC, Zijlstra A, Tkachenko E, Prager G, Gardel ML, Slepak M, Ginsberg MH.

CD98hc (SLC3A2) participates in fibronectin matrix assembly by mediating integrin


J Cell Biol. 2007 Aug 13;178(4):701-11.


Féral CC, Rose DM, Han J, Fox N, Silverman GJ,  Kaushansky K, Ginsberg MH

Blocking the alpha 4 integrin-paxillin interaction selectively impairs mononuclear

leukocyte recruitment to an inflammatory site.

J. Clin. Invest., 2006, Mar;116(3):715-23.


Feral CC, Nishiya N, Fenczik CA, Stuhlmann H, Slepak M, Ginsberg MH.

CD98hc (SLC3A2) mediates integrin signaling. 

Proc Natl Acad Sci USA., 2005, Jan 11;102(2):355-60.

(Feb 2016)

Financial Grants

Financial Grants