CD317 Promotes the survival of cancer cells through apoptosis-inducing factor

Abstract

BackgroundLow nutrient environment is a major obstacle to solid tumor growth. However, many tumors have developed adaptive mechanisms to circumvent the requirement for exogenous growth factors.MethodsHere we used siRNA interference or plasmid transfection techniques to knockdown or enhance CD317 expression respectively, in mammalian cancer cells, and subjected these CD317-manipulated cells to serum deprivation to study the role of CD317 on stress-induced apoptosis and the underlying mechanism.ResultsWe report that CD317, an innate immune gene overexpressed in human cancers, protected cancer cells against serum deprivation-induced apoptosis. In tumor cells, loss of CD317 markedly enhanced their susceptibility to serum deprivation-induced apoptosis with no effect on autophagy or caspase activation, indicating an autophagy- and caspase-independent mechanism of CD317 function. Importantly, CD317 knockdown in serum-deprived tumor cells impaired mitochondria function and subsequently promoted apoptosis-inducing factor (AIF) release and nuclear translocation but had little effect on mitochondrial and cytoplasmic distributions of cytochrome C, a pro-apoptotic factor released from mitochondria that initiates caspase processing in response to death stimuli. Furthermore, overexpression of CD317 in HEK293T cells inhibits serum deprivation-induced apoptosis as well as the release and nuclear accumulation of AIF.ConclusionOur data suggest that CD317 functions as an anti-apoptotic factor through the mitochondria-AIF axis in malnourished condition and may serve as a potential drug target for cancer therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0391-2) contains supplementary material, which is available to authorized users.

CD317 Activates EGFR by Regulating Its Association with Lipid Rafts

“…Neither knockdown nor overexpression of CD317 affected apoptosis ( Supplementary Fig. S1F and S1G), consistent with our previous observations (36).…”

“…siRNA-resistant (SR) CD317, delCT, and delGPI constructs, each tagged with HA, were generated via PCR by making three synonymous mutations in the siRNA recognition site of human CD317, and they are called HA-CD317-SR, HA-delCT-SR, and HA-delGPI-SR, respectively. Specific siRNA for human CD317 and nonspecific negative control were described previously (36). For stable transfection, two shRNAs targeting human CD317 (sh317) and control shRNA (shCtrl) were cloned into pLVTHM vectors.…”

Cell Surface Proteins in Hepatocellular Carcinoma: From Bench to Bedside

“…Li et al uncovered the anti-apoptotic function of BST2 in serum-starved Hep-G2 cells. The authors suggested that BST2 can be a useful target for combined antiangiogenic cancer therapies, since cancer cells can experience nutrient deprivation during progression and/or treatments that disrupt vascularization [92].…”

Ginsenoside Rh2 represses autophagy to promote cervical cancer cell apoptosis during starvation

“…A2 and promoting apoptosis in tumor cells [29]. To address whether Annexin A2 suppressed apoptosis following G-Rh2 treatment and serum deprivation, we forced Annexin A2 expression in HEK293T and detected its influence on apoptosis.…”