Kinesin superfamily proteins in cancer: unveiling their role in chemotherapy

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-09-27 DOI:10.1016/j.intimp.2025.115621

Hamza Abu Owida , Suleiman Ibrahim Mohammad , Asokan Vasudevan , Ashok Kumar Bishoyi , S. RenukaJyothi , Rajashree Panigrahi , Munthar Kadhim Abosaoda , Gunjan Garg , Amrita Pargaien

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引用次数: 0

Abstract

Kinesin superfamily proteins (KIFs) are driver proteins used by microtubules for intracellular transport, cellular homeostasis, and mitosis. Reportedly, the aberration in the expression of these proteins has been found to mediate sensitivity to chemotherapy. KIF5A, KIF11, and KIF20A are consistently involved in resistance to paclitaxel and docetaxel in breast, lung, and prostate cancers, while KIF14 overexpression is a prognostic marker for poor outcomes in paclitaxel-treated triple-negative breast and cervical cancer. KIF14 and KIF23 in HCC enhance sorafenib and cisplatin resistance, while suppression of KIF5B or KIF20A increases sensitivity to oxaliplatin in colorectal cancer. Clinic-applied fusions of KIF5B with ALK or EGFR have made it possible to use targeted therapy in non-small cell lung cancer. From a mechanistic point of view, PI3K/Akt, JAK/STAT, and NF-κB activation, metabolic reprogramming, and inhibition of cellular programmed death are involved in KIF-mediated resistance. KIF3A or KIF11 silencing increases chemosensitivity, suggesting a dual role here. Present approaches-small-molecule inhibitors, microRNA modulation, and KIF20A peptide vaccines-are hopeful but are beset by issues of toxicity and specificity. Overall, KIFs are context-dependent regulators of chemoresistance and are multifunctional but promising precision oncology targets.

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癌症中的运动蛋白超家族蛋白：揭示其在化疗中的作用

运动蛋白超家族蛋白（KIFs）是微管用于细胞内运输、细胞稳态和有丝分裂的驱动蛋白。据报道，已经发现这些蛋白表达的畸变介导了对化疗的敏感性。KIF5A、KIF11和KIF20A一直参与乳腺癌、肺癌和前列腺癌对紫杉醇和多西紫杉醇的耐药，而KIF14过表达是紫杉醇治疗的三阴性乳腺癌和宫颈癌预后不良的预后指标。HCC中KIF14和KIF23增强索拉非尼和顺铂耐药性，而抑制KIF5B或KIF20A则增加结直肠癌对奥沙利铂的敏感性。临床应用的KIF5B与ALK或EGFR的融合使得在非小细胞肺癌中使用靶向治疗成为可能。从机制的角度来看，PI3K/Akt、JAK/STAT和NF-κB的激活、代谢重编程和细胞程序性死亡的抑制参与了kif介导的耐药。KIF3A或KIF11沉默可增加化学敏感性，提示其具有双重作用。目前的方法——小分子抑制剂、microRNA调节和KIF20A肽疫苗——是有希望的，但受到毒性和特异性问题的困扰。总的来说，kif是化疗耐药的环境依赖性调节因子，是多功能但有前景的精确肿瘤靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.