Despite recent advances in targeted and immuno-therapy, metastasis still kills most cancer patients. Overcoming cancer metastasis requires a leap forward in understanding its molecular underpinnings to identify breakthrough therapeutic targets and strategies. A growing body of evidence suggests that specific subsets of cancer cells, which exhibit stem-like properties and are referred to as cancer stem cells (CSCs), are the primary drivers of cancer metastasis. How CSCs contribute to the multistep process of invasion and metastasis remains incompletely understood. Invadosomes are dynamic actin-based cellular protrusions that mediate cell invasion and pericellular proteolysis. Recent data have highlighted the highly proficient ability of CSCs to generate invadosomes, facilitating their local invasiveness, intravasation, extravasation, and metastatic colonization. This up-to-date and focused review describes the recent progress in characterizing invadosomes in embryonic cells during development and in CSCs during cancer metastasis. We summarize the molecular processes that regulate the invadosomes of CSCs. We discuss the molecules associated with the invadosome of CSCs and highlight their correlation with cancer metastasis in patients. We propose targeting the invadosomes of CSCs as a novel strategy to overcome cancer invasiveness and metastasis. This review highlights the emerging role of invadosomes in CSCs and provides a new perspective on pathobiology and cancer metastasis treatment.
