S100 proteins in cancer

Abstract

In humans, the S100 protein family is composed of 21 members that exhibit a high degree of structural similarity, but are not functionally interchangeable. This family of proteins modulates cellular responses by functioning both as intracellular Ca2+ sensors and as extracellular factors. Dysregulated expression of multiple members of the S100 family is a common feature of human cancers, with each type of cancer showing a unique S100 protein profile or signature. Emerging in vivo evidence indicates that the biology of most S100 proteins is complex and multifactorial, and that these proteins actively contribute to tumorigenic processes such as cell proliferation, metastasis, angiogenesis and immune evasion. Drug discovery efforts have identified leads for inhibiting several S100 family members, and two of the identified inhibitors have progressed to clinical trials in patients with cancer. This Review highlights new findings regarding the role of S100 family members in cancer diagnosis and treatment, the contribution of S100 signalling to tumour biology, and the discovery and development of S100 inhibitors for treating cancer.

S100A4 promotes colon inflammation and colitis-associated colon tumorigenesis

“…17 , 18 High S100A4 levels in colorectal tumors are associated with aggressive growth, metastasis, poor prognosis, and shortened patient survival times. 33 However, its role in colon cancer progression remains to be adequately tested.…”

“…17 , 18 Previous studies have reported that S100A4 is expressed in a variety of cells, such as fibroblasts, macrophages, and malignant cells, and plays a crucial role in mediating tumor-stromal interplay. 19-23 S100A4 functions as both intracellular and extracellular forms.…”

Un mécanisme d’activation cystéine-dépendant pour les ligands pro-inflammatoires de RAGE ?

“…La surexpression d'une dizaine de membres de la famille des protéines S100 a été mise en évidence dans différents types de cancers (côlon, prostate, poumons, sein, etc.) [5]. Cette surexpression est associée à des phénotypes incluant la croissance tumorale, l'angiogenèse, la métastase ou encore l'évasion immunitaire, par des mécanismes dépendant de RAGE [5,6].…”

“…Cette surexpression est associée à des phénotypes incluant la croissance tumorale, l'angiogenèse, la métastase ou encore l'évasion immunitaire, par des mécanismes dépendant de RAGE [5,6]. RAGE et les protéines S100 sont par conséquent considérés comme des cibles prometteuses pour le développement de nouvelles thérapies anti-cancéreuses [5]. Toutefois, plusieurs études récentes ont montré un rôle potentiellement béné-fique des interactions RAGE:S100 dans certains contextes cellulaires [4].…”

Structural Study on Apoptosis of Chronic Eosinophilic Leukemia Cells by Interaction of S100A8 with Splicing Factor, Proline and Glutamine-Rich

“…It is a main factor not only in the inflammatory response but also in breast, prostate, and thyroid cancers. Recently, S100A8 has been reported to be related to proliferation and metastasis of tumors (Bresnick et al, 2015). Research on the relation of S100A8 to leukemia has been actively studying, because it is known that S100A8 is regulated in the differentiation process of HL-60, a human Caucasian promyelocytic leukemia cell (Asakura et al, 2016;Yang et al, 2016).…”