Transcriptional Control of Metastasis by Integrated Stress Response Signaling

Si Lu; Li-Xian Yang; Zi-Jian Cao; Jiang-Sha Zhao; Jia You; Yu-Xiong Feng

doi:10.3389/fonc.2021.770843

Transcriptional Control of Metastasis by Integrated Stress Response Signaling

Front Oncol. 2021 Oct 20:11:770843. doi: 10.3389/fonc.2021.770843. eCollection 2021.

Authors

Si Lu^{1

2}, Li-Xian Yang^{1

2}, Zi-Jian Cao^{1

2}, Jiang-Sha Zhao^{1

2}, Jia You³, Yu-Xiong Feng^{1

2}

Affiliations

¹ Zhejiang Provincial Key Laboratory of Pancreatic Disease, First Affiliated Hospital, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China.
² Cancer Center, Zhejiang University, Hangzhou, China.
³ School of Life Sciences, Westlake University, Hangzhou, China.

Abstract

As a central cellular program to sense and transduce stress signals, the integrated stress response (ISR) pathway has been implicated in cancer initiation and progression. Depending on the genetic mutation landscape, cellular context, and differentiation states, there are emerging pieces of evidence showing that blockage of the ISR can selectively and effectively shift the balance of cancer cells toward apoptosis, rendering the ISR a promising target in cancer therapy. Going beyond its pro-survival functions, the ISR can also influence metastasis, especially via proteostasis-independent mechanisms. In particular, ISR can modulate metastasis via transcriptional reprogramming, in the help of essential transcription factors. In this review, we summarized the current understandings of ISR in cancer metastasis from the perspective of transcriptional regulation.

Keywords: EMT; cancer; integrated stress response (ISR); metastasis; transcription.

Publication types

Review