Your browser doesn't support javascript.
loading
MC1R regulates T regulatory cell differentiation through metabolic reprogramming to promote colon cancer.
Zhu, Shaoliang; Zou, Mengjie; Li, Chunxing; Tang, Yuntian; Luo, Honglin; Dong, Xiaofeng.
Afiliación
  • Zhu S; Department of Hepatobiliary, Pancreas and Spleen Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, China.
  • Zou M; Department of Nephrology, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, China.
  • Li C; Department of Operating Room, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, China.
  • Tang Y; Department of Hepatobiliary, Pancreas and Spleen Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, China. Electronic address: tangyuntian2021@163.com.
  • Luo H; Institute of Oncology, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, China. Electronic address: HLLUO4sci@126.com.
  • Dong X; Department of Hepatobiliary, Pancreas and Spleen Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, China. Electronic address: gandanyingcai@163.com.
Int Immunopharmacol ; 138: 112546, 2024 Jun 24.
Article en En | MEDLINE | ID: mdl-38917522
ABSTRACT

BACKGROUND:

Until 2021, colon cancer was a leading cancer globally. Early detection improves outcomes; however, advanced cases still having poor prognosis. Therefore, an understanding of associated molecular mechanisms is crucial for developing new preventive and therapeutic strategies for colon cancer.

METHODS:

The TCGA database was analyzed to assess melanocortin 1receptor (MC1R) expression in colon cancer and its link with patient prognosis. Further, models and diverse experimental techniques were employed to investigate the impact of MC1R on colon cancer progression and its underlying mechanism was elucidated.

RESULTS:

In a follow-up study of clinical patients, the important role of MC1R was identified in the development of colon cancer. First, MC1R was expressed more highly in colon tumor tissues than in adjacent tissues. In addition, MC1R was associated with colon cancer prognosis, and higher expression of MC1R tended to predict a worse prognosis. This conclusion was verified in MC1R-/- mice, which showed a greater resistance to tumor growth than wild-type mice, as expected. Further investigation revealed a significant change in the portion of Tregs in MC1R-/- mice, while the portion of CD4 + and CD8 + T cells remained unchanged. The in vitro experiments revealed a weaker ability of the MC1R-/- T cells to differentiate into Tregs. Previous studies report that the functional integrity of Tregs is interwoven with cellular metabolism. Therefore, MC1R was deduced to regulate the differentiation of Tregs by reprogramming the metabolism. As expected, MC1R-/- T cells exhibited weaker mitochondrial function and a lower aerobic oxidation capacity. Concurrently, the MC1R-/- T cells had stronger limiting effects on colon cancer cells. According to these results, the MC1R inhibitor was hypothesized as a potential therapeutic agent to suppress colon cancer. The results showed that upon MC1R suppression, the tumors in the mice developed more slowly, and the mice survived longer, potentially providing a novel strategy to treat clinical colon cancer.

CONCLUSION:

By regulating Tregs differentiation, MC1R overexpression in colon cancer correlates with poor prognosis, while MC1R inhibition shows potential as a therapeutic approach to slow tumor growth and enhance survival.
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China
...