Related Experiment Video

Updated: Nov 23, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

13.8K

Integrin αvβ6-TGFβ-SOX4 Pathway Drives Immune Evasion in Triple-Negative Breast Cancer

Archis Bagati1, Sushil Kumar2, Peng Jiang3

  • 1Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Smith Building, Room 736, 450 Brookline Avenue, Boston, MA 02215, USA; Department of Immunology, Harvard Medical School, Boston, MA 02215, USA; Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02215, USA.

Cancer Cell
|January 1, 2021
PubMed

Insights

Triple-negative breast cancer (TNBC) is resistant to immunotherapy due to SOX4. Blocking integrin αvβ6 sensitizes TNBC cells to T-cell therapy, improving survival in aggressive cancers.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Triple-negative breast cancer (TNBC) and other epithelial solid tumors often resist cancer immunotherapy.
  • Identifying resistance mechanisms is crucial for improving treatment efficacy.

Purpose of the Study:

  • To investigate the role of SOX4 transcription factor in TNBC resistance to T-cell-mediated cytotoxicity.
  • To explore the therapeutic potential of targeting the integrin αvβ6-TGFβ-SOX4 pathway.

Main Methods:

  • Investigated SOX4 function in TNBC cells.
  • Analyzed the regulation of SOX4 by integrin αvβ6 and TGFβ.
  • Utilized an integrin αvβ6-blocking monoclonal antibody (mAb) in preclinical TNBC models.

Main Results:

  • SOX4 acts as a resistance mechanism to T-cell-mediated cytotoxicity in TNBC.
  • Inactivating SOX4 enhances immune pathway gene expression in tumor cells.
  • Integrin αvβ6 blockade inhibits SOX4, sensitizing TNBC to cytotoxic T-cells.
  • The integrin mAb improved survival in metastatic TNBC models resistant to PD-1 blockade.

Conclusions:

  • Targeting the integrin αvβ6-TGFβ-SOX4 pathway offers a therapeutic strategy for TNBC.
  • This approach may benefit other aggressive epithelial cancers with limited immunotherapy response.
Keywords:
SOX4 transcription factorTGFβcancer immunotherapycytotoxic T cellsintegrin αvβ6therapy resistance

More Related Videos

Spheroid Assay to Measure TGF-β-induced Invasion09:18

Spheroid Assay to Measure TGF-β-induced Invasion

Published on: November 16, 2011

22.2K
Quantification of Breast Cancer Cell Invasiveness Using a Three-dimensional 3D Model08:08

Quantification of Breast Cancer Cell Invasiveness Using a Three-dimensional 3D Model

Published on: June 11, 2014

16.1K

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
9.5K
The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
7.3K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
2.6K
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.2K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
3.2K
Integrins01:10

Integrins

Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
4.8K