Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015:2015:352794.
doi: 10.1155/2015/352794. Epub 2015 Mar 3.

Calcium homeostasis and ER stress in control of autophagy in cancer cells

Elżbieta Kania  1 , Beata Pająk  2 , Arkadiusz Orzechowski  2
Affiliations
Review

Calcium homeostasis and ER stress in control of autophagy in cancer cells

Elżbieta Kania et al. Biomed Res Int. 2015.

Abstract

Autophagy is a basic catabolic process, serving as an internal engine during responses to various cellular stresses. As regards cancer, autophagy may play a tumor suppressive role by preserving cellular integrity during tumor development and by possible contribution to cell death. However, autophagy may also exert oncogenic effects by promoting tumor cell survival and preventing cell death, for example, upon anticancer treatment. The major factors influencing autophagy are Ca(2+) homeostasis perturbation and starvation. Several Ca(2+) channels like voltage-gated T- and L-type channels, IP3 receptors, or CRAC are involved in autophagy regulation. Glucose transporters, mainly from GLUT family, which are often upregulated in cancer, are also prominent targets for autophagy induction. Signals from both Ca(2+) perturbations and glucose transport blockage might be integrated at UPR and ER stress activation. Molecular pathways such as IRE 1-JNK-Bcl-2, PERK-eIF2α-ATF4, or ATF6-XBP 1-ATG are related to autophagy induced through ER stress. Moreover ER molecular chaperones such as GRP78/BiP and transcription factors like CHOP participate in regulation of ER stress-mediated autophagy. Autophagy modulation might be promising in anticancer therapies; however, it is a context-dependent matter whether inhibition or activation of autophagy leads to tumor cell death.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Autophagy mediated via ER stress and UPR activation. The figure represents proposed scheme for autophagy modulation in cancer cells through ER stress and UPR activation.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Gozuacik D., Kimchi A. Autophagy as a cell death and tumor suppressor mechanism. Oncogene. 2004;23(16):2891–2906. doi: 10.1038/sj.onc.1207521. - DOI - PubMed
    1. Wang S.-Y., Yu Q.-J., Zhang R.-D., Liu B. Core signaling pathways of survival/death in autophagy-related cancer networks. International Journal of Biochemistry and Cell Biology. 2011;43(9):1263–1266. doi: 10.1016/j.biocel.2011.05.010. - DOI - PubMed
    1. Nixon R. A. The role of autophagy in neurodegenerative disease. Nature Medicine. 2013;19(8):983–997. doi: 10.1038/nm.3232. - DOI - PubMed
    1. Vicencio J. M., Ortiz C., Criollo A., et al. The inositol 1,4,5-trisphosphate receptor regulates autophagy through its interaction with Beclin 1. Cell Death and Differentiation. 2009;16(7):1006–1017. doi: 10.1038/cdd.2009.34. - DOI - PubMed
    1. Hara T., Takamura A., Kishi C., et al. FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. The Journal of Cell Biology. 2008;181(3):497–510. doi: 10.1083/jcb.200712064. - DOI - PMC - PubMed

Publication types