La Trobe

STAT3 Signaling in Breast Cancer: Multicellular Actions and Therapeutic Potential

journal contribution
posted on 2022-09-16, 06:33 authored by SQ To, Rhynelle Sidney DmelloRhynelle Sidney Dmello, AK Richards, Matthias ErnstMatthias Ernst, Ashwini ChandAshwini Chand
Interleukin (IL)-6 family cytokines, such as IL-6 and IL-11, are defined by the shared use of the gp130 receptor for the downstream activation of STAT3 signaling and the activation of genes which contribute to the “hallmarks of cancer”, including proliferation, survival, invasion and metastasis. Increased expression of these cytokines, or the ligand-specific receptors IL-6R and IL-11RA, in breast tumors positively correlate to disease progression and poorer patient outcome. In this review, we examine evidence from pre-clinical studies that correlate enhanced IL-6 and IL-11 mediated gp130/STAT3 signaling to the progression of breast cancer. Key processes by which the IL-6 family cytokines contribute to the heterogeneous nature of breast cancer, immune evasion and metastatic potential, are discussed. We examine the latest research into the therapeutic targeting of IL-6 family cytokines that inhibit STAT3 transcriptional activity as a potential breast cancer treatment, including current clinical trials. The importance of the IL-6 family of cytokines in cellular processes that promote the development and progression of breast cancer warrants further understanding of the molecular basis for its actions to help guide the development of future therapeutic targets.

Funding

The study was supported by the following grants and fellowship schemes: National Breast Cancer Foundation (IIRS-19-066) and the Victorian Cancer Agency (19014). Institutional funding from the Victorian State Government Operational Infrastructure Support Scheme and ONJCRI is acknowledged. R.S.D. is supported by La Trobe University Full-Fee Research Scholarship and La Trobe University Postgraduate Research Scholarship.

History

Publication Date

2022-01-15

Journal

Cancers

Volume

14

Issue

2

Article Number

429

Pagination

20p.

Publisher

MDPI

ISSN

2072-6694

Rights Statement

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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