Research Papers:

The uncharacterized transcript KIAA0930 confers a cachexic phenotype on cancer cells

Takahiro Yamakawa _, Guoxiang Zhang, Liza Bengrine Najjar, Chun Li and Keiichi Itakura

PDF  |  Full Text  |  Supplementary Files  |  How to cite  |  Press Release

Oncotarget. 2023; 14:723-737. https://doi.org/10.18632/oncotarget.28476

Metrics: PDF 224 views  |   Full Text 982 views  |   ?  


Takahiro Yamakawa1, Guoxiang Zhang1, Liza Bengrine Najjar1, Chun Li1 and Keiichi Itakura1

1 Center for RNA Biology and Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA 91010, USA

Correspondence to:

Takahiro Yamakawa, email: [email protected]

Keywords: KIAA0930; cancer cachexia; muscle atrophy; inflammatory cytokines/chemokines; protein secretion

Received: May 24, 2023     Accepted: July 06, 2023     Published: July 20, 2023

Copyright: © 2023 Yamakawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Patients with cancer cachexia have a poor prognosis and impaired quality of life. Numerous studies using preclinical models have shown that inflammatory cytokines play an important role in the development of cancer cachexia; however, no clinical trial targeting cytokines has been successful. Therefore, it is essential to identify molecular mechanisms to develop anti-cachexia therapies. Here we identified the uncharacterized transcript KIAA0930 as a candidate cachexic factor based on analyses of microarray datasets and an in vitro muscle atrophy assay. While conditioned media from pancreatic, colorectal, gastric, and tongue cancer cells caused muscle atrophy in vitro, conditioned medium from KIAA0930 knockdown cells did not. The PANC-1 orthotopic xenograft study showed that the tibialis anterior muscle weight and cross-sectional area were increased in mice bearing KIAA0930 knockdown cells compared to control mice. Interestingly, KIAA0930 knockdown did not cause consistent changes in the secretion of inflammatory cytokines/chemokines from a variety of cancer cell lines. An initial characterization experiment showed that KIAA0930 is localized in the cytosol and not secreted from cells. These data suggest that the action of KIAA0930 is independent of the expression of cytokines/chemokines and that KIAA0930 could be a novel therapeutic target for cachexia.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 28476