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The unfolded protein response (UPR) pathway: the unsung hero in breast cancer management

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Abstract

Tumor cells always have the need to produce an increased amount of proteins in the cells. This elevated amount of proteins increases the pressure on the organelles of the cell such as the endoplasmic reticulum and compels it to increase its protein folding efficiency. However, it is by a matter of fact, that the amount of proteins synthesized outweighs the protein folding capacity of the ER which in turn switches on the UPR pathway by activating the three major molecular sensors and other signaling cascades, which helps in cell survival instead of instant death. However, if this pathway is active for a prolonged period of time the tumor cells heads toward apoptosis. Again, interestingly this is not the same as in case of non- tumorogenic cells. This exhibit a straight natural pathway for tumor cells-specific destruction which has a great implication in today’s world where hormone therapies and chemo-therapies are non-effective for various types of breast cancer, a major type being Triple Negative Breast Cancer. Thus a detailed elucidation of the molecular involvement of the UPR pathway in breast cancer may open new avenues for management and attract novel chemotherapeutic targets providing better hopes to patients worldwide.

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Abbreviations

GRP78:

Glucose regulated protein 78

UPR:

Unfolded Protein Response

TNBC:

Triple Negative Breast Cancer

PERK:

Protein kinase RNA-like endoplasmic reticulum kinase

ATF:

Activating transcription factor

IRE1:

Inositol Requiring Enzyme 1

ERS:

Endoplasmic Reticulum Stress

PAH:

Pulmonary Arterial Hypertension

SERM:

Selective Endoplasmic Reticulum Modulators

E2 :

17β-Estradiol

AI:

Aromatase Inhibitors

FDA:

Food and Drug Administration

PQC:

Protein Quality Control

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Acknowledgements

Authors would like to acknowledge the Department of Science and Technology, DST SERB (sanction no: SRG/2019/000259) and CSIR EMR grant file no. (27(0359)/20/EMR-II) for financial support. Authors sincerely acknowledge Dr Rudranil De, for grammatical editing of the manuscript.

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  1. Amity Institute of Biotechnology, Amity University, Major Arterial Road, Action Area II, Rajarhat, Newtown, Kolkata, West Bengal, 700135, India

    Arunita Patra & Swatilekha Ghosh

  2. Department of Life Science and Biotechnology, Jadavpur University, 188, Raja Subodh Chandra Mallick Road, Jadavpur, Kolkata, West Bengal, 700032, India

    Arghya Adhikary

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AP, AA, SG wrote the paper and designed the figures; Concept and hypothesis AA and SG

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Patra, A., Adhikary, A. & Ghosh, S. The unfolded protein response (UPR) pathway: the unsung hero in breast cancer management. Apoptosis 28, 263–276 (2023). https://doi.org/10.1007/s10495-022-01803-3

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