School of Life Sciences, Central University of Gujarat, Gandhinagar, Gujarat 382030, India.
Special Center for Molecular medicine, Jawaharlal Nehru University, New Delhi 110067, India.
Life Sci. 2022 Sep 1;304:120706. doi: 10.1016/j.lfs.2022.120706. Epub 2022 Jun 9.
Obesity has reached a pandemic proportion and is responsible for the augmentation of multimorbidity including certain cancers. With the rise in obesity amongst the female population globally, a concomitant increase in breast cancer (BC) incidence and related mortality has been observed. In the present review, we have elucidated the cellular and molecular insight into the visfatin-mediated cellular plasticity programs such as Epithelial to mesenchymal transition (EMT) and Endothelial to mesenchymal transition (EndoMT), and stemness-associated changes in BC cells. EMT and EndoMT are responsible for inducing metastasis in cancer cells and conferring chemotherapy resistance, immune escape, and infinite growth potential. Visfatin, an obesity-associated adipokine implicated in metabolic syndrome, has emerged as a central player in BC pathogenesis. Several studies have indicated the presence of visfatin in the tumor microenvironment (TME) where it augments EMT and EndoMT of BC cells. Further, Visfatin also modulates the TME by acting on the tumor stroma cells such as adipocytes, infiltrated immune cells, and adipose-associated stem cells that secrete factors such as cytokines, and extracellular vesicles responsible for augmenting cellular plasticity program. Visfatin induced altered metabolism of the cancer cells and molecular determinants such as non-coding RNAs involved in EMT and EndoMT have been discussed. We have also highlighted specific therapeutic targets that can be exploited for the development of effective BC treatment. Taken together, these advanced understandings of cellular and molecular insight into the visfatin-mediated cellular plasticity programs may stimulate the development of better approaches for the prevention and therapy of BC, especially in obese patients.
肥胖已达到流行程度，并导致多种疾病的增加，包括某些癌症。随着全球女性人口中肥胖的增加，乳腺癌（BC）的发病率和相关死亡率也观察到相应增加。在本综述中，我们阐明了内脂素介导的细胞可塑性程序（如上皮间质转化（EMT）和内皮间质转化（EndoMT））以及 BC 细胞中的干性相关变化的细胞和分子见解。EMT 和 EndoMT 负责诱导癌细胞转移，并赋予其化疗耐药性、免疫逃逸和无限生长潜力。内脂素是一种与代谢综合征相关的肥胖相关脂肪因子，已成为 BC 发病机制中的关键因素。几项研究表明，内脂素存在于肿瘤微环境（TME）中，它增强了 BC 细胞的 EMT 和 EndoMT。此外，内脂素还通过作用于肿瘤基质细胞（如脂肪细胞、浸润的免疫细胞和脂肪相关干细胞）来调节 TME，这些细胞会分泌细胞因子和细胞外囊泡等因子，从而增强细胞可塑性程序。内脂素诱导癌细胞代谢改变以及 EMT 和 EndoMT 涉及的非编码 RNA 等分子决定因素也已被讨论。我们还强调了可以用于开发有效的 BC 治疗的特定治疗靶点。总之，对内脂素介导的细胞可塑性程序的细胞和分子见解的深入了解，可能会促进更好的预防和治疗 BC 的方法的发展，特别是在肥胖患者中。
