Osteopontin promotes integrin activation through outside-in and inside-out mechanisms: OPN-CD44V interaction enhances survival in gastrointestinal cancer cells.

Osteopontin (OPN) and splice variants of CD44 (CD44(V)) have independently been identified as markers for tumor progression. In this study, we show that both OPN and CD44(V) are frequently overexpressed in human gastric cancer and that OPN-engaged CD44(V) ligation confers cells an increased survival mediated through integrin activation. First, we show that OPN treatment confers cells an increased resistance to UV-induced apoptosis. The OPN-mediated antiapoptosis is dependent on the expression of the variant exon 6 (V6)- or V7-containing CD44 as shown by overexpression of individual CD44(V) in gastric AZ521 cells that express no or very low level of endogenous CD44 and by knockdown of the constitutively expressed V6-containing CD44 isoforms in colon HT29 cells. Although OPN also interacts with RGD integrins, OPN-RGD sequence is dispensable for OPN-mediated antiapoptosis. OPN-induced antiapoptosis is mainly attributed to the engagement of CD44(V) isoforms and the relay of an inside-out signaling via Src activity, leading to robust integrin activation. Furthermore, OPN-elicited antiapoptosis was observed when cells were plated on fibronectin but not on poly-D-lysin, and preincubation of cells with anti-integrin beta(1) antibody to block integrin-extracellular matrix (ECM) interaction or ectopic expression of the dominant-negative forms of focal adhesion kinase to block ECM-derived signal abolished OPN-induced survival, suggesting that OPN-elicited antiapoptotic function is propagated from matrix transduced by integrin. Taken together, we showed that OPN-CD44(V) interaction promotes ECM-derived survival signal mediated through integrin activation, which may play an important role in the pathogenic development and progression of gastric cancer.

Lee JL ，Wang MJ ，Sudhir PR ，Chen GD ，Chi CW ，Chen JY ... -  《CANCER RESEARCH》

Alpha-V-dependent outside-in signaling is required for the regulation of CD44 surface expression, MMP-2 secretion, and cell migration by osteopontin in human melanoma cells.

Samanna V ，Wei H ，Ego-Osuala D ，Chellaiah MA ... -  《EXPERIMENTAL CELL RESEARCH》

The involvement of osteopontin and its receptors in multiple myeloma cell survival, migration and invasion in the murine 5T33MM model.

Caers J ，Günthert U ，De Raeve H ，Van Valckenborgh E ，Menu E ，Van Riet I ，Van Camp B ，Vanderkerken K ... -  《BRITISH JOURNAL OF HAEMATOLOGY》

Differential regulation of osteopontin receptors, CD44 and the alpha(v) and beta(3) integrin subunits, in the rat hippocampus following transient forebrain ischemia.

Kang WS ，Choi JS ，Shin YJ ，Kim HY ，Cha JH ，Lee JY ，Chun MH ，Lee MY ... -  《BRAIN RESEARCH》

Activation of JAK2/STAT3 signaling by osteopontin promotes tumor growth in human breast cancer cells.

Behera R ，Kumar V ，Lohite K ，Karnik S ，Kundu GC ... -  《-》