Metastasis and cancer associated fibroblasts: taking it up a NOTCH

Argha Ghosh; Anirban K Mitra

doi:10.3389/fcell.2023.1277076

Metastasis and cancer associated fibroblasts: taking it up a NOTCH

Front Cell Dev Biol. 2024 Jan 10:11:1277076. doi: 10.3389/fcell.2023.1277076. eCollection 2023.

Authors

Argha Ghosh^{1

2}, Anirban K Mitra^{1

2

3}

Affiliations

¹ Indiana University School of Medicine-Bloomington, Bloomington, IN, United States.
² Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, United States.
³ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States.

Abstract

Metastasis is the least understood aspect of cancer biology. 90% of cancer related deaths occur due extensive metastatic burden in patients. Apart from metastasizing cancer cells, the pro-tumorigenic and pro-metastatic role of the tumor stroma plays a crucial part in this complex process often leading to disease relapse and therapy resistance. Cellular signaling processes play a crucial role in the process of tumorigenesis and metastasis when aberrantly turned on, not just in the cancer cells, but also in the cells of the tumor microenvironment (TME). One of the most conserved pathways includes the Notch signaling pathway that plays a crucial role in the development and progression of many cancers. In addition to its well documented role in cancer cells, recent evidence suggests crucial involvement of Notch signaling in the stroma as well. This review aims to highlight the current findings focusing on the oncogenic role of notch signaling in cancer cells and the TME, with a specific focus on cancer associated fibroblasts (CAFs), which constitute a major part of the tumor stroma and are important for tumor progression. Recent efforts have focused on the development of anti-cancer and anti-metastatic therapies targeting TME. Understanding the importance of Notch signaling in the TME would help identify important drivers for stromal reprogramming, metastasis and importantly, drive future research in the effort to develop TME-targeted therapies utilizing Notch.

Keywords: Notch signaling; cancer associated fibroblasts; cancer metastasis; ovarian cancer; tumor microenvironment.

Publication types

Review

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. AM was funded by American Cancer Society Research Scholar Grant (RSG-21-019-01-CSM) and Department of Defense IIRG (HT9425-23-1-0605).