Yin Zihao, Su Rongyu, Long Shengwen, Chen Guo, Xiang Shuanglin
The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Science, Hunan Normal University, No. 36, Lushan Road, Yuelu District, Changsha 410081, China.
State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, No. 36, Lushan Road, Yuelu District, Changsha 410081, China.
Integr Biol (Camb). 2025 Jan 8;17. doi: 10.1093/intbio/zyaf014.
Colorectal cancer is a highly prevalent malignant tumor of the digestive tract worldwide. Immunotherapy has emerged as a critical therapeutic approach for CRC patients. We observed that KCTD10 expression is significantly downregulated in colorectal cancer tissues compared to normal tissues, and patients with higher KCTD10 expression exhibited prolonged survival. To investigate its functional role, we established stable KCTD10-overexpressing CT26 and SW480 colorectal cancer cell lines. Both in vitro and in vivo experiments demonstrated that KCTD10 overexpression suppresses colorectal cancer progression and inhibits the EMT process. Notably, KCTD10 overexpression upregulated PD-L1 expression and synergistically enhanced the therapeutic efficacy of anti-PD-1 treatment. Our findings reveal that KCTD10 functions as a tumor suppressor in colorectal cancer pathogenesis. Mechanistically, KCTD10 potentiates the antitumor efficacy of anti-PD-1 immunotherapy by upregulating PD-L1 expression, thereby proposing a novel therapeutic target and suggesting a promising combination strategy for CRC treatment. Insight box KCTD10 can inhibit the development of colorectal cancer and the EMT process. And the over-expression of KCTD10 increased the expression of PD-L1, improved the efficacy of PD-1 treatment.
结直肠癌是全球范围内一种高度普遍的消化道恶性肿瘤。免疫疗法已成为结直肠癌患者的关键治疗方法。我们观察到，与正常组织相比，结直肠癌组织中KCTD10的表达显著下调，且KCTD10表达较高的患者生存期延长。为了研究其功能作用，我们建立了稳定过表达KCTD10的CT26和SW480结直肠癌细胞系。体外和体内实验均表明，KCTD10过表达可抑制结直肠癌进展并抑制上皮-间质转化（EMT）过程。值得注意的是，KCTD10过表达上调了PD-L1的表达，并协同增强了抗PD-1治疗的疗效。我们的研究结果表明，KCTD10在结直肠癌发病机制中起着肿瘤抑制作用。机制上，KCTD10通过上调PD-L1表达增强了抗PD-1免疫疗法的抗肿瘤疗效，从而提出了一个新的治疗靶点，并为结直肠癌治疗提示了一种有前景的联合策略。见解框：KCTD10可抑制结直肠癌的发展和EMT过程。并且KCTD10的过表达增加了PD-L1的表达，提高了PD-1治疗的疗效。
