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Transcriptional Control of Metastasis by Integrated Stress Response Signaling

Si Lu1,2, Li-Xian Yang1,2, Zi-Jian Cao1,2

  • 1Zhejiang Provincial Key Laboratory of Pancreatic Disease, First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.

Frontiers in Oncology
|November 8, 2021
PubMed

Insights

The integrated stress response (ISR) pathway impacts cancer progression and metastasis. Targeting the ISR shows promise in cancer therapy by inducing apoptosis and modulating transcriptional reprogramming for metastasis.

Area of Science:

  • Cellular biology
  • Cancer research
  • Molecular oncology

Background:

  • The integrated stress response (ISR) pathway is a crucial cellular mechanism for sensing and responding to stress.
  • The ISR pathway plays a significant role in cancer initiation and progression.
  • Emerging evidence suggests the ISR pathway can be therapeutically targeted in cancer.

Purpose of the Study:

  • To review the current understanding of the ISR pathway's role in cancer metastasis.
  • To explore the mechanisms by which the ISR influences metastasis, particularly proteostasis-independent pathways.
  • To focus on the transcriptional regulation aspects of ISR in cancer metastasis.

Main Methods:

  • Literature review of existing research on the ISR pathway and cancer metastasis.
  • Analysis of studies investigating the ISR's role in transcriptional reprogramming.
  • Synthesis of findings related to transcription factors involved in ISR-mediated metastasis.

Main Results:

  • The ISR pathway influences cancer metastasis through mechanisms beyond its pro-survival functions.
  • Proteostasis-independent mechanisms are involved in ISR-mediated metastasis.
  • Transcriptional reprogramming, guided by key transcription factors, is a significant way the ISR modulates metastasis.

Conclusions:

  • The ISR pathway is a promising therapeutic target in cancer, with potential to induce apoptosis.
  • Understanding the ISR's role in metastasis, especially via transcriptional regulation, is crucial for developing novel cancer therapies.
  • Targeting ISR-mediated transcriptional reprogramming may offer new strategies to combat cancer metastasis.
Keywords:
EMTcancerintegrated stress response (ISR)metastasistranscription

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