Kallioniemi Anne
Institute of Biomedical Technology/BioMediTech, University of Tampere and Fimlab Laboratories, Finland.
Cancer Genet. 2012 Jun;205(6):267-77. doi: 10.1016/j.cancergen.2012.05.009.
Bone morphogenetic proteins (BMPs) are extracellular signaling molecules that belong to the transforming growth factor β (TGFβ) superfamily and are well-known for their indispensable roles in vertebrate development. In recent years, important new information has been generated on the contribution of BMP family members, such as BMP4, in cancer pathogenesis. First of all, BMP4 gene variants have been shown to predispose to colorectal cancer. In sporadic cancer, BMP4 expression levels are commonly altered in many tumor types and have been linked to patient prognosis in hepatocellular and ovarian cancer. In terms of BMP4 function in cancer cells, the majority of studies demonstrate that BMP4 suppresses cell growth both in vitro and in vivo, and at the same time is able to induce migration, invasion, and epithelial-mesenchymal transition. These latter phenotypes are typically associated with cancer metastasis and progression, and thus BMP4 seems to elicit effects that are both detrimental and beneficial for the cancer cells. The functional effects of BMP4 are not restricted to the control of cell proliferation and mobility, since it also contributes to the regulation of differentiation, apoptosis, and angiogenesis. The latter is especially intriguing since the formation of new blood vessels is a prerequisite for sustained tumor growth and cancer progression. Mainly due to its growth suppressive abilities, BMP4 has been suggested as a possible therapeutic target in cancer cells. However, the other functional characteristics of BMP4, especially the promotion of cell mobility, make such strategies less appealing. Improved knowledge of the downstream mediators of BMP4 effects in cancer cells may allow dissection of the different BMP4-induced phenotypes and thereby generation of specific targeted therapies.
骨形态发生蛋白（BMPs）是细胞外信号分子，属于转化生长因子β（TGFβ）超家族，因其在脊椎动物发育中不可或缺的作用而闻名。近年来，关于BMP家族成员，如BMP4，在癌症发病机制中的作用产生了重要的新信息。首先，已表明BMP4基因变异易患结直肠癌。在散发性癌症中，BMP4表达水平在许多肿瘤类型中通常会发生改变，并与肝细胞癌和卵巢癌患者的预后相关。就BMP4在癌细胞中的功能而言，大多数研究表明，BMP4在体外和体内均抑制细胞生长，同时能够诱导迁移、侵袭和上皮-间质转化。后几种表型通常与癌症转移和进展相关，因此BMP4似乎对癌细胞产生了有害和有益的影响。BMP4的功能作用不仅限于控制细胞增殖和迁移，因为它还参与分化、凋亡和血管生成的调节。后者尤其引人关注，因为新血管的形成是肿瘤持续生长和癌症进展的先决条件。主要由于其生长抑制能力，BMP4被认为是癌细胞中可能的治疗靶点。然而，BMP4的其他功能特性，尤其是促进细胞迁移，使得这些策略吸引力降低。更好地了解BMP4在癌细胞中作用的下游介质，可能有助于剖析不同的BMP4诱导表型，从而产生特异性靶向治疗方法。
