Plk2 Loss Commonly Occurs in Colorectal Carcinomas but not Adenomas: Relationship to mTOR Signaling

Elizabeth M. Matthew, Zhaohai Yang, Suraj Peri, Mark Andrake, Roland Dunbrack, Eric Ross, Wafik S. El-Deiry

Research output: Contribution to journalArticle

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Abstract

Plk2 is a target of p53. Our previous studies demonstrated that with wild-type p53, Plk2 impacts mTOR signaling in the same manner as TSC1, and Plk2-deficient tumors grew larger than control. Other investigators have demonstrated that Plk2 phosphorylates mutant p53 in a positive feedback loop. We investigated Plk2’s tumor suppressor functions in relationship to mTOR signaling. Archival specimens from 12 colorectal adenocarcinomas were stained for markers including Plk2, phosphorylated mTOR (serine 2448) and ribosomal S6 (Serine 235/236). We show that Plk2 is expressed in normal colon, with a punctate staining pattern in supranuclear cytoplasm. In colorectal adenocarcinoma, Plk2 demonstrates complete or partial loss of expression. Strong expression of phosphorylated mTOR is observed in the invasive front. Phosphorylated S6 expression partially correlates with phosphorylated mTOR expression but appears more diffuse in some cases. p53 and Ki67 expression is diffuse, in the subset of cases examined. In order to determine whether Plk2 is lost prior to the development of invasive cancer, 8 colon polyps from 6 patients were evaluated for Plk2 expression. All polyps are positive for Plk2. A Cancer Genome Atlas search identified Plk2 mutations to be infrequent in colorectal adenocarcinomas. Neither Plk2 methylation (in the gene body) nor copy number variations correlated with changes in mRNA expression levels. Loss of Plk2 expression along with accentuated expression of phosphorylated mTOR and phosphorylated S6 at the invasive front in some colorectal carcinomas is consistent with previous findings that an interaction between Plk2 and TSC1 / mTOR signaling molecules plays a role in tumor suppression. Plk2 protein expression is lost at the same stage in colorectal carcinogenesis as p53. The p53 dependence of Plk2 loss and tumor suppressor function in relationship to mTOR signaling may have therapeutic implications.

Original languageEnglish (US)
Pages (from-to)244-255
Number of pages12
JournalNeoplasia (United States)
Volume20
Issue number3
DOIs
StatePublished - Mar 1 2018

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Adenoma
Colorectal Neoplasms
S 6
Adenocarcinoma
Neoplasms
Polyps
Serine
Atlases
Colonic Neoplasms
Methylation
Colon
Carcinogenesis
Cytoplasm
Research Personnel
Genome
Staining and Labeling
Messenger RNA
Mutation
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Matthew, E. M., Yang, Z., Peri, S., Andrake, M., Dunbrack, R., Ross, E., & El-Deiry, W. S. (2018). Plk2 Loss Commonly Occurs in Colorectal Carcinomas but not Adenomas: Relationship to mTOR Signaling. Neoplasia (United States), 20(3), 244-255. https://doi.org/10.1016/j.neo.2018.01.004
Matthew, Elizabeth M. ; Yang, Zhaohai ; Peri, Suraj ; Andrake, Mark ; Dunbrack, Roland ; Ross, Eric ; El-Deiry, Wafik S. / Plk2 Loss Commonly Occurs in Colorectal Carcinomas but not Adenomas : Relationship to mTOR Signaling. In: Neoplasia (United States). 2018 ; Vol. 20, No. 3. pp. 244-255.
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Matthew, EM, Yang, Z, Peri, S, Andrake, M, Dunbrack, R, Ross, E & El-Deiry, WS 2018, 'Plk2 Loss Commonly Occurs in Colorectal Carcinomas but not Adenomas: Relationship to mTOR Signaling', Neoplasia (United States), vol. 20, no. 3, pp. 244-255. https://doi.org/10.1016/j.neo.2018.01.004

Plk2 Loss Commonly Occurs in Colorectal Carcinomas but not Adenomas : Relationship to mTOR Signaling. / Matthew, Elizabeth M.; Yang, Zhaohai; Peri, Suraj; Andrake, Mark; Dunbrack, Roland; Ross, Eric; El-Deiry, Wafik S.

In: Neoplasia (United States), Vol. 20, No. 3, 01.03.2018, p. 244-255.

Research output: Contribution to journalArticle

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T1 - Plk2 Loss Commonly Occurs in Colorectal Carcinomas but not Adenomas

T2 - Relationship to mTOR Signaling

AU - Matthew, Elizabeth M.

AU - Yang, Zhaohai

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AU - Andrake, Mark

AU - Dunbrack, Roland

AU - Ross, Eric

AU - El-Deiry, Wafik S.

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