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Understanding the role of integrins in breast cancer invasion, metastasis, angiogenesis, and drug resistance

Oncogene volume 40, pages 1043–1063 (2021)Cite this article

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Abstract

Integrins are cell adhesion receptors, which are typically transmembrane glycoproteins that connect to the extracellular matrix (ECM). The function of integrins regulated by biochemical events within the cells. Understanding the mechanisms of cell growth by integrins is important in elucidating their effects on tumor progression. One of the major events in integrin signaling is integrin binding to extracellular ligands. Another event is distant signaling that gathers chemical signals from outside of the cell and transmit the signals upon cell adhesion to the inside of the cell. In normal breast tissue, integrins function as checkpoints to monitor effects on cell proliferation, while in cancer tissue these functions altered. The combination of tumor microenvironment and its associated components determines the cell fate. Hypoxia can increase the expression of several integrins. The exosomal integrins promote the growth of metastatic cells. Expression of certain integrins is associated with increased metastasis and decreased prognosis in cancers. In addition, integrin-binding proteins promote invasion and metastasis in breast cancer. Targeting specific integrins and integrin-binding proteins may provide new therapeutic approaches for breast cancer therapies. This review will examine the current knowledge of integrins’ role in breast cancer.

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Fig. 1: Integrin heterodimers consists of an alpha (α) and a beta (β) subunit associated by noncovalent interactions forming an extracellular ligand-binding part, two multi-domain, two single-pass transmembrane helices and two short cytoplasmic tails.
Fig. 2: Integrin inside–out and outside–in signaling.
Fig. 3: Integrin and integrin-associated proteins promote therapy-resistance in breast cancer.
Fig. 4: Integrin signaling promotes metastasis in breast cancer.

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  1. These authors contributed equally: Hassan Yousefi, Mousa Vatanmakanian, Mojdeh Mahdiannasser

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, LSUHSC, School of Medicine, New Orleans, LA, USA

    Hassan Yousefi, Mousa Vatanmakanian & Suresh K. Alahari

  2. Department of Medical Genetics, Tehran University of Medical Sciences, School of Medicine, Tehran, Iran

    Mojdeh Mahdiannasser

  3. University of Arkansas for Medical Sciences, Little Rock, AK, USA

    Ladan Mashouri

  4. Louisiana State University, Baton Rouge, LA, USA

    Nikhilesh V. Alahari

  5. T cell memory laboratory, Department of Immunology, Shiraz University of Medical Sciences, Shiraz, Iran

    Mohammad Rafiee Monjezi

  6. Department of Medical Genetics, Shiraz University of Medical Sciences, Shiraz, Iran

    Shahrzad Ilbeigi

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Yousefi, H., Vatanmakanian, M., Mahdiannasser, M. et al. Understanding the role of integrins in breast cancer invasion, metastasis, angiogenesis, and drug resistance. Oncogene 40, 1043–1063 (2021). https://doi.org/10.1038/s41388-020-01588-2

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