1. Academic Validation
  2. MICAL1 facilitates pancreatic cancer proliferation, migration, and invasion by activating WNT/β-catenin pathway

MICAL1 facilitates pancreatic cancer proliferation, migration, and invasion by activating WNT/β-catenin pathway

  • J Transl Med. 2022 Nov 12;20(1):528. doi: 10.1186/s12967-022-03749-1.
Kun Cai # 1 2 3 4 Lu Deng # 5 Dijie Zheng # 1 6 3 4 Lin Li 1 6 3 4 Zhiwei He 7 8 Chao Yu 9 10 11 12
Affiliations

Affiliations

  • 1 Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of Guizhou Medical University, No.28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou, China.
  • 2 College of Clinical Medicine, Guizhou Medical University, Guiyang, China.
  • 3 Guizhou Provincial Institute of Hepatobiliary, Pancreatic and Splenic Diseases, Guiyang, China.
  • 4 Key Laboratory of Liver, Gallbladder, Pancreas and Spleen, Guizhou Medical University, Guiyang, China.
  • 5 Guizhou Provincial Staff Hospital, Guiyang, China.
  • 6 College of Basic Medicine, Guizhou Medical University, Guiyang, China.
  • 7 Department of Hepatobiliary Surgery, Shenzhen Key Laboratory, Shenzhen University General Hospital, Xueyuan AVE 1098, Nanshan District, Shenzhen, 518055, Guangdong, China. [email protected].
  • 8 Shenzhen University Clinical Medical Academy Center, Shenzhen University, Shenzhen, China. [email protected].
  • 9 Department of Hepatic-Biliary-Pancreatic Surgery, The Affiliated Hospital of Guizhou Medical University, No.28 Guiyi Street, Yunyan District, Guiyang, 550001, Guizhou, China. [email protected].
  • 10 College of Clinical Medicine, Guizhou Medical University, Guiyang, China. [email protected].
  • 11 Guizhou Provincial Institute of Hepatobiliary, Pancreatic and Splenic Diseases, Guiyang, China. [email protected].
  • 12 Key Laboratory of Liver, Gallbladder, Pancreas and Spleen, Guizhou Medical University, Guiyang, China. [email protected].
  • # Contributed equally.
Abstract

Background: MICAL1 is involved in the malignant processes of several types of cancer; however, the role of MICAL1 in pancreatic Cancer (PC) has not been well-characterized. This study aimed to investigate the expression and function of MICAL1 in PC.

Methods: RT-qPCR and immunohistochemistry were used to detect MICAL1 expression in PC and adjacent nontumor tissues. Cell Counting Kit-8, EdU, clone formation, wound healing, and Transwell assays as well as animal models were used to investigate the effects of overexpression or inhibition of MICAL1 expression on the proliferation, invasion, and metastasis of PC cells. RNA-seq was used to explore the main pathway underlying the functions of MICAL1. Proteomics, mass spectrometry, and co-immunoprecipitation assays were used to investigate the interaction of proteins with MICAL1. Rescue experiments were conducted to validate these findings.

Results: Both MICAL1 mRNA and protein levels were upregulated in PC tissues compared with matched adjacent nontumor tissues. The expression level of MICAL1 was associated with the proliferative and metastatic status of PC. Repression of MICAL1 significantly inhibited PC cell growth, migration, and invasion in vitro and in vivo. RNA sequencing analysis indicated that MICAL1 was closely correlated with the Wnt pathway. Overexpression of MICAL1 (1) promoted the phosphorylation of TBC1D1 at the Ser660 site, (2) facilitated the distribution of FZD7 on the cytomembrane, (3) inhibited the degradation of FZD7 in the lysosome, and (4) activated the Wnt pathway.

Conclusions: MICAL1 was upregulated in PC and involved in stimulating the progression of PC cells by activating the Wnt/β-catenin signaling pathway. Therefore, MICAL1 is a potential therapeutic target for PC.

Keywords

FZD7; MICAL1; Pancreatic cancer; TBC1D1; WNT pathway.

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