# A Transcriptional Variant of Anaplastic Lymphoma Kinase Promotes Apoptosis in Ovarian High‐Grade Serous Carcinoma

## TL;DR

A new variant of the ALK gene promotes cell death in ovarian cancer cells, possibly through interaction with a DNA repair protein.

## Contribution

The study identifies a novel ALK transcript, ALKATI, and its role in inducing apoptosis in ovarian high-grade serous carcinoma.

## Key findings

- ALKATI localizes to both the cytoplasm and nucleus in HGSC cells, unlike full-length ALK.
- ALKATI increases sensitivity to cisplatin-induced apoptosis and interacts with PARP1.
- ALKATI reduces epithelial-mesenchymal transition and cancer stem cell properties without affecting proliferation.

## Abstract

The current study aims to delineate the role of a novel anaplastic lymphoma kinase (ALK) transcript, ALKATI, in ovarian high‐grade serous carcinoma (HGSC). Overexpressed ALKATI exhibited both cytoplasmic and nuclear localization in HGSC cells, whereas full‐length ALK was predominantly cytoplasmic. ALKATI interacts with the DNA repair protein, poly (ADP ribose) polymer 1 (PARP1), and cells stably overexpressing ALKATI (OE‐ ALKATI) were more sensitive to cisplatin‐induced apoptosis. Consistent with this, cleaved PARP1 levels were higher in HGSC tissue samples in areas with nuclear ALK immunoreactivity. The ratio of antiapoptotic BCL2 relative to proapoptotic BAX was significantly increased in OE‐ALKATI cells, despite the increase in apoptosis, suggesting that ALKATI‐mediated apoptosis is independent of mitochondrion‐driven cell death. OE‐ALKATI decreased epithelial‐mesenchymal transition/cancer stem cell properties but did not alter proliferation rates, and nuclear ALK immunopositivity was not associated with clinicopathological factors or prognosis in HGSC. Together, our observations suggest that ALKATI sensitizes HGSC cells to apoptosis (probably though an association with PARP1) but this may have a relatively minor impact on tumor progression.