2. Academic Validation
  3. Loss of wild-type p53 promotes mutant p53-driven metastasis through acquisition of survival and tumor-initiating properties

Loss of wild-type p53 promotes mutant p53-driven metastasis through acquisition of survival and tumor-initiating properties

  • Nat Commun. 2020 May 11;11(1):2333. doi: 10.1038/s41467-020-16245-1.
Mizuho Nakayama 1 2,  Chang Pyo Hong 3,  Hiroko Oshima 1 2,  Eri Sakai 1,  Seong-Jin Kim 3 4,  Masanobu Oshima 5 6
Affiliations

Affiliations

  • 1 Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, 920-1192, Japan.
  • 2 WPI Nano Life Science Institute, Kanazawa University, Kanazawa, 920-1192, Japan.
  • 3 Theragen Etex Bio Institute, Suwon, 16229, Republic of Korea.
  • 4 Precision Medicine Research Center, Advanced Institute of Convergence Technology and Department of Transdisciplinary Studies, Seoul National University, Suwon, 16229, Republic of Korea.
  • 5 Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, 920-1192, Japan. oshimam@staff.kanazawa-u.ac.jp.
  • 6 WPI Nano Life Science Institute, Kanazawa University, Kanazawa, 920-1192, Japan. oshimam@staff.kanazawa-u.ac.jp.
PMID: 32393735 DOI: 10.1038/s41467-020-16245-1
Abstract

Missense-type mutant p53 plays a tumor-promoting role through gain-of-function (GOF) mechanism. In addition, the loss of wild-type TP53 through loss of heterozygosity (LOH) is widely found in Cancer cells. However, malignant progression induced by cooperation of TP53 GOF mutation and LOH remains poorly understood. Here, we show that mouse intestinal tumors carrying Trp53 GOF mutation with LOH (AKTPM/LOH) are enriched in metastatic lesions when heterozygous Trp53 mutant cells (AKTP+/M) are transplanted. We show that Trp53 LOH is required for dormant cell survival and clonal expansion of Cancer cells. Moreover, AKTPM/LOH cells show an increased in vivo tumor-initiating ability compared with AKTPNull and AKTP+/M cells. RNAseq analyses reveal that inflammatory and growth factor/MAPK pathways are specifically activated in AKTPM/LOH cells, while the stem cell signature is upregulated in both AKTPM/LOH and AKTPNull cells. These results indicate that TP53/Trp53 LOH promotes TP53/Trp53 GOF mutation-driven metastasis through the activation of distinct pathway combination.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z