美国加州大学Paul S. Mischel课题组的一项最新研究发现，生长因子信号通路中的癌基因扩增导致膜脂质重塑依赖性的癌症。这一研究成果于2019年9月3日发表在《细胞—代谢》上。

他们表示溶血磷脂酰胆碱酰基转移酶LPCAT1功能性地将癌症中的特定遗传改变，与异常代谢和质膜重塑联系起来以驱动肿瘤生长。研究发现生长因子受体驱动的癌症依赖于LPCAT1通过增强的饱和磷脂酰胆碱含量来塑造质膜组成，而饱和磷脂酰胆碱含量又是转录致癌信号所必需的。这些结果指向基因型知情策略，其优先考虑脂质重塑途径作为多种癌症的治疗靶标。

据介绍，DNA测序技术的进步重塑了我们对癌症分子基础的理解，提供了精确的肿瘤基因组视图。癌症的互补生物化学和生物物理学观点指向营养摄取和利用的明显改变推动肿瘤生长和肿瘤细胞质膜结构的主要变化。弥合肿瘤生物学这些基本方面的分子机制仍然知之甚少。

附：英文原文

Title: Oncogene Amplification in Growth Factor Signaling Pathways Renders Cancers Dependent on Membrane Lipid Remodeling

Author: Benjamin F. Cravatt, Paul S. Mischel,et al

Issue&Volume: Volume 30 Issue 3

Abstract: Advances in DNA sequencing technologies have reshaped our understanding of the molecular basis of cancer, providing a precise genomic view of tumors. Complementary biochemical and biophysical perspectives of cancer point toward profound shifts in nutrient uptake and utilization that propel tumor growth and major changes in the structure of the plasma membrane of tumor cells. The molecular mechanisms that bridge these fundamental aspects of tumor biology remain poorly understood. Here, we show that the lysophosphatidylcholine acyltransferase LPCAT1 functionally links specific genetic alterations in cancer with aberrant metabolism and plasma membrane remodeling to drive tumor growth. Growth factor receptor-driven cancers are found to depend on LPCAT1 to shape plasma membrane composition through enhanced saturated phosphatidylcholine content that is, in turn, required for the transduction of oncogenic signals. These results point to a genotype-informed strategy that prioritizes lipid remodeling pathways as therapeutic targets for diverse cancers.

DOI: https://doi.org/10.1016/j.cmet.2019.06.014

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30317-1#