IRCCS Istituto Ortopedico Galeazzi, Via R. Galeazzi 4, 20161 Milano, Italy.
Int J Mol Sci. 2020 Feb 5;21(3):1051. doi: 10.3390/ijms21031051.
The most serious aspect of neoplastic disease is the spread of cancer cells to secondary sites. Skeletal metastases can escape detection long after treatment of the primary tumour and follow-up. Bone tissue is a breeding ground for many types of cancer cells, especially those derived from the breast, prostate, and lung. Despite advances in diagnosis and therapeutic strategies, bone metastases still have a profound impact on quality of life and survival and are often responsible for the fatal outcome of the disease. Bone and the bone marrow environment contain a wide variety of cells. No longer considered a passive filler, bone marrow adipocytes have emerged as critical contributors to cancer progression. Released by adipocytes, adipokines are soluble factors with hormone-like functions and are currently believed to affect tumour development. Src-associated in mitosis of 68 kDa (Sam68), originally discovered as a protein physically associated with and phosphorylated by c-Src during mitosis, is now recognised as an important RNA-binding protein linked to tumour onset and progression of disease. Sam68 also regulates splicing events and recent evidence reports that dysregulation of these events is a key step in neoplastic transformation and tumour progression. The present review reports recent findings on adipokines and Sam68 and their role in breast cancer progression and metastasis.
肿瘤疾病最严重的方面是癌细胞向继发性部位扩散。即使在原发肿瘤和后续治疗后很久，骨骼转移也可能逃脱检测。骨骼组织是许多类型癌细胞的滋生地，尤其是那些源自乳腺、前列腺和肺部的癌细胞。尽管在诊断和治疗策略方面取得了进展，但骨骼转移仍然对生活质量和生存产生深远影响，并且常常是导致疾病致命结局的原因。骨骼和骨髓环境中包含着各种各样的细胞。骨髓脂肪细胞不再被视为被动填充剂，而是作为癌症进展的关键贡献者出现。脂肪细胞释放的脂肪因子是具有激素样功能的可溶性因子，目前被认为会影响肿瘤的发展。Src 相关在有丝分裂 68 kDa（Sam68）最初被发现是一种在有丝分裂过程中与 c-Src 物理相关并被其磷酸化的蛋白质，现在被认为是一种与肿瘤发生和疾病进展相关的重要 RNA 结合蛋白。Sam68 还调节剪接事件，最近的证据表明，这些事件的失调是肿瘤转化和肿瘤进展的关键步骤。本综述报告了关于脂肪因子和 Sam68 的最新发现，以及它们在乳腺癌进展和转移中的作用。
