Chaudhary Sanjib, Siddiqui Jawed Akhtar, Pothuraju Ramesh, Bhatia Rakesh
Jyoti and Bhupat Mehta School of Health Sciences and Technology, Indian Institute of Technology Guwahati, 781039, Guwahati, Assam, India.
Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS, USA; Cancer Center Research Institute, University of Mississippi Medical Center, Jackson, MS, USA.
Cancer Lett. 2025 Mar 1;612:217484. doi: 10.1016/j.canlet.2025.217484. Epub 2025 Jan 20.
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with a poor overall survival rate. Cellular stress response pathways promoting cancer cell fitness in harsh tumor microenvironment (TME) play a critical role in cancer growth and survival. The influence of oncogenic Kras, multi-functional heterogeneous cancer-associated fibroblasts (CAFs), and immunosuppressive TME on cancer cells makes the disease more complex and difficult to treat. The desmoplastic reaction by CAFs comprises approximately 90 % of the tumor, with only 10 % of cancer cells making things even more complicated, resulting in therapy resistance. Consistently increasing fibrosis creates a hypoxic environment and elevated interstitial fluid pressure inside the tumor constraining vascular supply. Stress conditions in TME alter translation efficiency and metabolism to fulfill the energy requirements of rapidly growing cancer cells. Extensive research has been conducted on multiple molecular and metabolic regulators in PDAC TME. However, the role of TME in influencing translation programs, a prerequisite for cell cycle progression and functional/growth requirements for cancer cells, remains elusive. This review highlights the recent advancements in understanding altered translational programs in PDAC TME. We emphasize the role of ribosome biogenesis, ribosome-induced stress response, and the concept of specialized ribosomes and their probable role in mutationally rewiring the pancreatic TME.
胰腺导管腺癌（PDAC）是一种致命的恶性肿瘤，总体生存率较低。在恶劣的肿瘤微环境（TME）中促进癌细胞适应性的细胞应激反应途径在癌症的生长和存活中起着关键作用。致癌性Kras、多功能异质性癌症相关成纤维细胞（CAF）和免疫抑制性TME对癌细胞的影响使该疾病更加复杂且难以治疗。CAF引起的促纤维增生反应约占肿瘤的90%，只有10%的癌细胞，这使得情况更加复杂，导致治疗耐药。持续增加的纤维化会形成缺氧环境，并提高肿瘤内部的间质液压力，从而限制血管供应。TME中的应激条件会改变翻译效率和代谢，以满足快速生长的癌细胞的能量需求。人们已经对PDAC TME中的多种分子和代谢调节因子进行了广泛研究。然而，TME在影响翻译程序方面的作用，这是细胞周期进展以及癌细胞功能/生长需求的先决条件，仍然难以捉摸。本综述重点介绍了在理解PDAC TME中改变的翻译程序方面的最新进展。我们强调核糖体生物发生、核糖体诱导的应激反应的作用，以及特殊核糖体的概念及其在突变性重塑胰腺TME中的可能作用。
