S100P interacts with integrin α7 and increases cancer cell migration and invasion in lung cancer

Abstract

S100P, a Ca2+ binding protein, has been shown to be overexpressed in various cancers. However, its functional character in lung cancer remains largely unknown. In this study, we show that S100P increases cancer migration, invasion and metastasis in lung cancer cells. Ectopic expression of S100P increases migration, invasion and EMT in less invasive CL1-0 lung cancer cells. Conversely, knockdown of S100P suppressed migration and invasion, and caused a reversion of EMT in highly invasive lung cancer cells. These effects were transduced by increasing the interaction of S100P with integrin α7, which activated focal adhesion kinase (FAK) and AKT. Blocking FAK significantly decreased S100P-induced migration by decreasing Src and AKT activation, whereas inhibiting AKT reduced S100P upregulation on ZEB1 expression. Further study has indicated that S100P knockdown prevents the spread of highly metastatic human lung cancer in animal models. This study therefore suggests that S100P represents a critical activator of lung cancer metastasis. Detection and targeted treatment of S100P-expressing cancer is an attractive therapeutic strategy in treating lung cancer.

Predictive value of integrin α7 for acute myeloid leukemia risk and its correlation with prognosis in acute myeloid leukemia patients

“…In order to investigate the role of ITGA7 in AML patients, we herein enrolled 196 de novo AML patients as well as 50 controls, and we discovered that both ITGA7 mRNA and protein expressions were higher in AML patients compared to controls. One possible reason was that ITGA7 interacted with FAK/Akt signaling and Syk/SATA signaling axis to promote AML cell survival and proliferation, which subsequently caused high risk of AML . Another reason was that ITGA7 could increase leukemia stem cells (LSC) properties including self‐renew through mediating various pathways (such as activating the FAK‐mediated signaling pathways and interacting with FMS‐like tyrosine kinase‐3), thereby contributed to the increased AML risk .…”

“…As one of common members of the integrin family, ITGA7 is a kind of primary extracellular matrix receptor and could use its β1 chain to form heterodimers, subsequently transducing signals from the matrix to cells, which has been discovered to promote tumor progression of different carcinomas via multiple pathways . For instance, an appealing study shows that ITGA7 binds with S100P to activate focal adhesion kinase (FAK)/serine protein kinase (AKT)‐ zinc finger E‐box Binding Homeobox 1 (ZEB1) signaling way, which thereby promotes cell migration and cell invasion in lung cancer . Another recent report provides strong in vitro and in vivo evidence that ITGA7 interacts with laminin‐induced outside‐in signaling to participant in the growth and invasion of glioblastoma stem‐like cells .…”

Interplay between Trx‐1 and S100P promotes colorectal cancer cell epithelial–mesenchymal transition by up‐regulating S100A4 through AKT activation

“…| 2437 S100P could promote cancer invasion and metastasis by promoting the EMT in CRC 48,50 and lung cancer. 21 In this study, we saw that the down-regulation of S100P or Trx-1 inhibited S100A4 expression, whereas overexpression of S100P or Trx-1 promoted S100A4 expression. Down-regulation of S100A4 expression by siRNA reversed S100P-and Trx-1-induced EMT, migration and invasion of CRC cells.…”

“…62 S100P could also activate AKT signalling in lung cancer cells. 21 Indeed, we observed that blocking AKT signalling partially reversed S100P-or Trx-1induced S100A4 expression, EMT, and migration and invasion of CRC cells. Therefore, we speculate that AKT signalling may be involved in S100A4 up-regulation and EMT mediated by S100P or Trx-1.…”

“…[16][17][18] S100P expression is up-regulated in various cancers and has an important role in tumour growth, invasion and metastasis. [19][20][21] In our previous studies, we found that overexpression of Trx-1 or S100P enhances CRC cell invasion and metastasis, and conversely, suppression of Trx-1 or S100P expression inhibits CRC cell invasion and metastasis. 15,19,22 We also reported that both Trx-1 and S100P expressions are up-regulated in CRC and correlates with CRC invasion and metastasis.…”