Expression of hippo pathway in colorectal cancer

Saudi J Gastroenterol. 2014 May-Jun;20(3):188-94. doi: 10.4103/1319-3767.133025.

Abstract

Background/aims: Hippo pathway plays a crucial role in cell proliferation, apoptosis, and tumorigenesis. This study aimed to investigate the expression of Hippo pathway components in the progression and metastasis of colorectal cancer (CRC).

Materials and methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the mRNA expression levels of MST1, LATS2, YAP, TAZ, TEAD1, CDX2, and OCT4, and western blot (WB) was used to examine the protein expression levels of MST1, YAP, TEAD1, and CDX2 in 30 specimens of human colorectal adenomas, 50 pairs of human CRC tissues, and adjacent nontumorous tissues from CRC patients. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was used as the housekeeping gene in qRT-PCR.

Results: The mRNA expression levels of MST1 and LATS2 showed an increasing tendency from CRC to adjacent nontumorous tissues (P < 0.001). Conversely, the mRNA expression levels of YAP, TAZ, TEAD, and OCT4 showed a decreasing tendency from CRC to adjacent nontumorous tissues (P < 0.001). MST1 protein was downregulated and YAP and TEAD1 proteins were upregulated in CRC (all P < 0.001). The mRNA and protein expression levels of CDX2 in CRC were significantly lower than those in colorectal adenomas and adjacent nontumorous tissues (P < 0.001), but there was no significant difference between the latter two groups (qRT-PCR, P = 0.113; WB, P = 0.151). Furthermore, statistical analysis showed that the expression levels of Hippo signal pathway components were associated with tumor differentiation, lymph node metastasis, and TNM stage.

Conclusion: Hippo pathway is suppressed in the progression from colorectal adenomas to CRC and is associated with CRC progression and metastasis. This study suggests the components of Hippo pathway might be prognostic indicators for CRC patients.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenoma / genetics*
  • Adenoma / pathology
  • Adult
  • Aged
  • Analysis of Variance
  • Apoptosis / genetics
  • Blotting, Western
  • CDX2 Transcription Factor
  • Carcinogenesis / genetics
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic / genetics*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hepatocyte Growth Factor / metabolism*
  • Hippo Signaling Pathway
  • Homeodomain Proteins / metabolism
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Octamer Transcription Factor-3 / metabolism
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Sampling Studies
  • Signal Transduction / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Up-Regulation

Substances

  • CDX2 Transcription Factor
  • CDX2 protein, human
  • Homeodomain Proteins
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • macrophage stimulating protein
  • Hepatocyte Growth Factor
  • LATS2 protein, human
  • Protein Serine-Threonine Kinases