Oncotarget


CEMIP upregulates BiP to promote breast cancer cell survival in hypoxia


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The cover for issue 42 of Oncotarget features Figure 6, "Model for CEMIP-mediated upregulation of BiP leading to increased cell survival during hypoxia/stress," by Banach, et al

Here we show that CEMIP mediates activation of the Bi P promoter and upregulates Bi P transcript and protein levels in breast cancer cell lines.

Reducing Bi P in CEMIP-expressing cells sensitized cells to hypoxia treatment, decreased glucose uptake, and resulted in tumor regression in vivo.

Dr. Richard Z. Lin from the Department of Physiology and Biophysics Institute of Molecular Cardiology at Stony Brook University in Stony Brook, NY, USA as well as the Medical Service at the Northport Veterans Affairs Medical Center in Northport, NY, USA said, "The results presented in this study provide strong evidence that CEMIP upregulates Bi P at the transcriptional level to mediate resistance to tumor microenvironments often characterized by oxygen and nutrient depletion."

Figure 6: Model for CEMIP-mediated upregulation of BiP leading to increased cell survival during hypoxia/stress.

Figure 6: Model for CEMIP-mediated upregulation of BiP leading to increased cell survival during hypoxia/stress. HIF-2α and NF-κB accumulate in cells exposed to hypoxia or other stresses and bind directly to the CEMIP promoter. Increased CEMIP levels result in CEMIP-mediated activation of the BiP promoter by an unknown mechanism. Upregulation of BiP protein leads to activation of protective pathways such as increased autophagy and glucose uptake as well as decreased apoptosis. CEMIP is also activating another undetermined pro-survival mechanism independent of BiP.

CEMIP forms a stable complex with Bi P in the ER, leading to enhanced cell migration.

In addition to its canonical function in the ER, Bi P was also found to play a critical role in cancer progression by promoting cancer cell survival, proliferation, migration, and chemoresistance.

Other reports indicate that Bi P is induced in cancer cells in response to hypoxia and serves a protective function by means of activating autophagy.

Based on these collective findings, we hypothesized that CEMIP promotes cell survival in hypoxic conditions by upregulating Bi P expression.

Identifying the correlation between CEMIP and Bi P expression as well as the protective functions that they provide to cancer cells exposed to hypoxia could lead to the development of more efficient chemotherapeutics.

The Lin research team concluded, "The results presented in this study provide strong evidence that CEMIP upregulates Bi P at the transcriptional level to mediate resistance to tumor microenvironments often characterized by oxygen and nutrient depletion."

Full text - https://doi.org/10.18632/oncotarget.27036

Correspondence to - Richard Z. Lin - [email protected]

Keywords - CEMIP, BiP, hypoxia, autophagy



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