Ievgenia Pastushenko

Highlights • Primary skin SCCs with EMT have a high incidence of metastasis • Primary skin SCCs without EMT have no metastasis • Circulating tumor cells present EMT in primary tumors with metastasis • Transplanted tumors present metastasis regardless of EMT Summary Epithelial-to-mesenchymal transition (EMT) has been proposed to be important for metastatic dissemination. However, recent studies have challenged the requirement of EMT for metastasis.

Nieto M.A. et al. EMT: 2016. Cell. 2016; 166: 21-45 Brabletz T. To differentiate or not – routes towards metastasis. Nat. Rev. Cancer. 2012; 12: 425-436 De Craene B. Berx G. Regulatory networks defining EMT during cancer initiation and progression. Nat. Rev. Cancer. 2013; 13: 97-110 Puisieux A. et al. Oncogenic roles of EMT-inducing transcription factors. Nat. Cell Biol. 2014; 16: 488-494 Huang R.Y. et al.

Our traditional understanding of phenotypic plasticity in adult somatic cells comprises dedifferentiation and transdifferentiation in the context of tissue regeneration or wound healing. Although dedifferentiation is central to tissue repair and stemness, this process inherently carries the risk of cancer initiation. Consequently, recent research suggests phenotypic plasticity as a new paradigm for understanding cancer initiation, progression, and resistance to therapy.