Cardiothoracic Dept., Section of Respiratory System Diseases, IRCCS Policlinico San Matteo, Pavia, Italy.
Candiolo Cancer Institute, FPO-IRCCS, Str Prov 142, 10060 Candiolo, Italy.
EBioMedicine. 2017 Oct;24:34-42. doi: 10.1016/j.ebiom.2017.09.025. Epub 2017 Sep 21.
The molecular and cellular mechanisms which drive metastatic spread are the topic of constant debate and scientific research due to the potential implications for cancer patients' prognosis. In addition to genetics and environmental factors, mechanics of single cells and physical interaction with the surrounding environment play relevant role in defining invasive phenotype. Reconstructing the physical properties of metastatic clones may help to clarify still open issues in disease progression as well as to lead to new diagnostic and therapeutic approaches. In this perspective cancer of unknown primary origin (CUP) identify the ideal model to study physical interactions and forces involved in the metastatic process. We have previously demonstrated that MET oncogene is mutated with unexpected high frequency in CUPs. We here analyze and discuss how the MET activation by somatic mutation may affect physical properties in giving rise to such a highly malignant syndrome, as that defined by CUP.
驱动转移扩散的分子和细胞机制是一个持续争论和科学研究的主题，因为这对癌症患者的预后有潜在影响。除了遗传和环境因素外，单细胞力学和与周围环境的物理相互作用在定义侵袭表型方面也起着重要作用。重建转移克隆的物理特性可能有助于澄清疾病进展中仍然存在的问题，并导致新的诊断和治疗方法。从这个角度来看，不明原发灶癌（CUP）是研究转移过程中涉及的物理相互作用和力的理想模型。我们之前已经证明，MET 癌基因在 CUP 中以出人意料的高频突变。在这里，我们分析和讨论了体细胞突变激活 MET 如何影响物理特性，从而导致这种高度恶性的综合征，如 CUP 所定义的那样。
