# Molecular Mechanisms Underlying Cell Survival During Endoplasmic Reticulum Stress

> **NIH NIH SC3** · CALIFORNIA STATE UNIVERSITY LONG BEACH · 2021 · $110,625

## Abstract

ABSTRACT
Endoplasmic reticulum (ER) stress is a form of cellular stress that is experienced by our cells both
under normal physiological conditions such as in professional secretory cells and disease states
such as cancer, diabetes and neurodegeneration. Upon facing ER stress, cells initially attempt to
restore normal function by activating a conserved signaling pathway called the unfolded protein
response (UPR). However, if the stress becomes chronic and homeostasis is not restored within
a reasonable timeframe, the UPR ultimately commits cells to programmed cell death. How cells
make this life-or-death decision remains an exciting yet poorly understood phenomenon. Cancer
cells exhibit ER stress due to their high rates of glucose metabolism and hypoxic conditions
resulting in accumulation of underglycosylated, misfolded proteins in the ER. The ability of cancer
cells to successfully adapt to ER stress and continue to survive has been correlated to their
invasiveness/malignancy and chemoresistance. Thus, to be able to design effective molecularly
targeted therapeutic strategies, it is crucial to delineate the mechanisms that endow cancer cells
with cytoprotection in the face of ER stress. The main objective of this proposal is to investigate
the molecular mechanisms that play a decisive role in promoting cell survival through ER stress.
With the central hypothesis that the pro-survival Akt pathway regulates the UPR to determine the
overall cell fate, we will (A) Aim 1: investigate the role of Akt in regulation of signals originating
from the UPR sensors in response to stress (B) Aim 2: determine the mechanism by which Akt is
activated in a non-canonical manner during ER stress. Our results will potentially lead to important
revelations as to how cancer cells gain a cytoprotective advantage during ER stress resulting in
prolonged survival. The successful completion of our proposal will advance the field in terms of
enhancing our fundamental knowledge of a fascinating cell biological process as well as finding
new and key targets for curbing cancer cell survival.

## Key facts

- **NIH application ID:** 10089988
- **Project number:** 1SC3GM139707-01
- **Recipient organization:** CALIFORNIA STATE UNIVERSITY LONG BEACH
- **Principal Investigator:** Deepali Bhandari
- **Activity code:** SC3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $110,625
- **Award type:** 1
- **Project period:** 2021-05-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10089988

## Citation

> US National Institutes of Health, RePORTER application 10089988, Molecular Mechanisms Underlying Cell Survival During Endoplasmic Reticulum Stress (1SC3GM139707-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10089988. Licensed CC0.

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