Cell Adhesion and Matrix Stiffness: Coordinating Cancer Cell Invasion and Metastasis

Abstract

Metastasis is a multistep process in which tumor extracellular matrix (ECM) and cancer cell cytoskeleton interactions are pivotal. ECM is connected, through integrins, to the cell’s adhesome at cell–ECM adhesion sites and through them to the actin cytoskeleton and various downstream signaling pathways that enable the cell to respond to external stimuli in a coordinated manner. Cues from cell-adhesion proteins are fundamental for defining the invasive potential of cancer cells, and many of these proteins have been proposed as potent targets for inhibiting cancer cell invasion and thus, metastasis. In addition, ECM accumulation is quite frequent within the tumor microenvironment leading in many cases to an intense fibrotic response, known as desmoplasia, and tumor stiffening. Stiffening is not only required for the tumor to be able to displace the host tissue and grow in size but also contributes to cell–ECM interactions and can promote cancer cell invasion to surrounding tissues. Here, we review the role of cell adhesion and matrix stiffness in cancer cell invasion and metastasis.

Impact of prolonged and early bevacizumab treatment on the overall survival of EGFR‐mutant and EGFR‐wild type nonsquamous non‐small cell lung cancer

“…The manifold composition of stromal cells, immune cells, and molecular factors in the microenvironment of non‐small cell lung cancer (NSCLC) plays a significant role in supporting initiation, progression, and metastasis . VEGF, one of the crucial molecular factors stimulating angiogenesis and extracellular matrix remodeling, has been shown to take a central part in the development of a wide array of solid cancer types .…”

“…The manifold composition of stromal cells, immune cells, and molecular factors in the microenvironment of non-small cell lung cancer (NSCLC) plays a significant role in supporting initiation, progression, and metastasis. [1][2][3] VEGF, one of the crucial molecular factors stimulating angiogenesis and extracellular matrix remodeling, has been shown to take a central part in the development of a wide array of solid cancer types. 1,4,5 Recently, with increasing knowledge of the effects of inducing inhibitory checkpoint proteins and of promoting the accumulation of myeloid-derived suppressor and T-regulatory cells in tumor milieu, the immunosuppressive property of VEGF has also been recognized.…”

Circulating tumor cells and the metastatic process: the complexity of malignancy

“…Primary tumor-derived CTCs, with a mesenchymal expression profile and an elongated cell shape that allows them to adhere on ECM substrate and direct their migration, are able to penetrate in the blood stream [82] . Once reached a desirable metastatic niche, CTCs promote disruption of cell adhesion and polarity, remodeling of the cytoskeleton and changes in cell-ECM adhesion [83,84] . This tissue remodeling process leads to the generation of crossing points relevant for migration and tissue invasion [77] .…”

Optimal stimulation frequency for vibrational optical coherence elastography

“…Stiffness is one of the most important mechanical properties of human tissue, which is closely related to pathological conditions [1], it severs as a signature to distinguish benign and lesion tissue in clinics, for instance, prostate cancer [2] and breast cancer [3]. This functional imaging modality explores stiffness contrast is termed as elastography.…”