The overexpression of protein interacting with carboxyl terminus 1 (PICT-1) in medullary thyroid carcinoma (MTC) cells increases their viability, found a new study published in the Journal of Neuroendocrinology.

Notably, PICT-1 overexpression also completely reverses the reduction in cell viability that is caused by everolimus, a mammalian target of rapamycin (mTOR) inhibitor that is often used to treat patients with progressive neuroendocrine neoplasms.

“These findings suggest a possible role of PICT-1 . . . in the complex network of mTOR,” the study authors wrote. This finding “may have relevance for the therapeutic efficacy in tumor types for which treatment with mTOR inhibitors is indicated,” they added.


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To explore the potential role of PICT-1 in the tumorigenesis of neuroendocrine neoplasms and the response to mTOR inhibitors, a team of researchers led by Hadara Rubinfeld, PhD, from Tel Aviv University Sackler School of Medicine in Petach Tikva, Israel, conducted experiments in which they overexpressed PICT-1 in medullary thyroid and pancreatic neuroendocrine neoplasm cell lines.

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While PICT-1 overexpression had no effect in pancreatic cells, it induced the appearance of p53β lacking the C-terminus end and resulted in a big decrease in the expression of the cell cycle inhibitor p21.

When they examined the mTOR pathway in these cells, the researchers saw that PICT-1 overexpression led to a reduction in the expression of the tumor suppressor PTEN. It also resulted in a large increase in phospho-Akt-Ser473 expression, which is a downstream effector of PI3K, which PTEN negatively regulates. This effect was only partially inhibited by everolimus treatment.

The increase in phospho-Akt-Ser473 level and the downregulation of p21 could explain the increase in cellular viability, the researchers said.

Reference

Bareli Y, Shimon I, Tobar A, Rubinfeld H. PICT-1 regulates p53 splicing and sensitivity of medullary thyroid carcinoma cells to everolimus. J Neuroendocrinol. Published online October 15, 2022. doi:10.1111/jne.13187