S100A11 is required for efficient plasma membrane repair and survival of invasive cancer cells

Abstract

Cell migration and invasion require increased plasma membrane dynamics and ability to navigate through dense stroma, thereby exposing plasma membrane to tremendous physical stress. Yet, it is largely unknown how metastatic cancer cells acquire an ability to cope with such stress. Here we show that S100A11, a calcium-binding protein up-regulated in a variety of metastatic cancers, is essential for efficient plasma membrane repair and survival of highly motile cancer cells. Plasma membrane injury-induced entry of calcium into the cell triggers recruitment of S100A11 and Annexin A2 to the site of injury. We show that S100A11 in a complex with Annexin A2 helps reseal the plasma membrane by facilitating polymerization of cortical F-actin and excision of the damaged part of the plasma membrane. These data reveal plasma membrane repair in general and S100A11 and Annexin A2 in particular, as new targets for the therapy of metastatic cancers.

Knockdown of BC200 RNA expression reduces cell migration and invasion by destabilizing mRNA for calcium-binding protein S100A11

“…[19][20][21][22][23] It is overexpressed in a large variety of invasive carcinomas, and its suppression substantially decreases cell migration. 21,23 Therefore, the reduced motility of siBC200-transfected HeLa cells could result from the BC200 RNA-knockdown-induced downregulation of S100A11. Shown are Mock-siNegative (red), Mock-siBC200 I (pale red), CBC200-siNegative (blue) and CBC200-siBC200 I (pale blue) (mean § SD; n D 3; Ã P < 0.05, by Student's ttest).…”

“…Since BC200 RNA is highly expressed in some breast cancer cells [19][20][21][22][23] we also analyzed the connection between BC200 RNA, cell motility, and S100A11 expression (Fig 9). We found that the BC200 RNA knockdown decreased the wound-healing rate.…”

“…[19][20][21][22][23] This calciumbinding protein is known to promote cellular motility by maintaining outer membrane integrity. [19][20][21][22][23] Ribosome profiling showed reducing expression of S100A11 following BC200 knockdown. Further analysis revealed that S100A11 was reduced at both the mRNA and protein levels following BC200 RNA knockdown, suggesting that the reduced footprints mainly resulted from the downregulation of mRNA.…”

S100 and annexin proteins identify cell membrane damage as the Achilles heel of metastatic cancer cells

“…[10][11][12] While much of the focus has been on disease resulting from poor PMR, we have recently identified that improved PMR is an important contributor for cancer metastasis. 13 Human breast cancer cells that turn metastatic through Keywords: actin, annexins, Annexin A2, breast cancer, cancer, plasma membrane repair, S100 proteins, S100A11, Metastasis up-regulation of truncated EGF receptor (ErbB2) also need to up-regulate their PMR machinery, and absence of enhanced PMR compromises their invasive ability. Here we will briefly discuss the mechanisms involved in PMR, with a focus on the involvement of annexins, actin and S100 proteins.…”

“…We recently identified this to be the case, as PM of invasive cancer cells suffered greater damage. 13 In response, we find these invasive cancer cells enhance their PMR by up regulating expression of S100A11 and annexin A2 proteins. 13 Annexins and S100 proteins are commonly up regulated in variety of cancers.…”