Niche Modulation of IGF-1R Signaling: Its Role in Stem Cell Pluripotency, Cancer Reprogramming, and Therapeutic Applications

Pei-Chin Chen; Yung-Che Kuo; Cheng-Ming Chuong; Yen-Hua Huang

doi:10.3389/fcell.2020.625943

Niche Modulation of IGF-1R Signaling: Its Role in Stem Cell Pluripotency, Cancer Reprogramming, and Therapeutic Applications

Front Cell Dev Biol. 2021 Jan 12:8:625943. doi: 10.3389/fcell.2020.625943. eCollection 2020.

Authors

Pei-Chin Chen^{1

2

3}, Yung-Che Kuo⁴, Cheng-Ming Chuong⁵, Yen-Hua Huang^{2

4

6

7

8

9

10

11}

Affiliations

¹ Department of Education, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
² Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
³ Department of Internal Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
⁴ TMU Research Center of Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei, Taiwan.
⁵ Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
⁶ International Ph.D. Program for Cell Therapy and Regeneration Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁷ Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁸ TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan.
⁹ Center for Reproductive Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei, Taiwan.
¹⁰ Comprehensive Cancer Center of Taipei Medical University, Taipei, Taiwan.
¹¹ PhD Program for Translational Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.

Abstract

Stem cells work with their niches harmoniously during development. This concept has been extended to cancer pathology for cancer stem cells (CSCs) or cancer reprogramming. IGF-1R, a classical survival signaling, has been shown to regulate stem cell pluripotency, CSCs, or cancer reprogramming. The mechanism underlying such cell fate determination is unclear. We propose the determination is due to different niches in embryo development and tumor malignancy which modulate the consequences of IGF-1R signaling. Here we highlight the modulations of these niche parameters (hypoxia, inflammation, extracellular matrix), and the targeted stem cells (embryonic stem cells, germline stem cells, and mesenchymal stem cells) and CSCs, with relevance to cancer reprogramming. We organize known interaction between IGF-1R signaling and distinct niches in the double-sided cell fate with emerging trends highlighted. Based on these new insights, we propose that, through targeting IGF-1R signaling modulation, stem cell therapy and cancer stemness treatment can be further explored.

Keywords: IGF-1R; cancer stemness; extracellular matrix; hypoxia; inflammation; niche; stem cells.

Publication types

Review