Next Article in Journal
Recent Progress in Mitochondria-Targeted Drug and Drug-Free Agents for Cancer Therapy
Next Article in Special Issue
Systemic Actions of Breast Cancer Facilitate Functional Limitations
Previous Article in Journal
Metabolic Alterations in Pancreatic Cancer Progression
Previous Article in Special Issue
ER Stress and Unfolded Protein Response in Cancer Cachexia
Open AccessArticle

Upregulation of ZIP14 and Altered Zinc Homeostasis in Muscles in Pancreatic Cancer Cachexia

1
Institute for Cancer Genetics, Columbia University Irving Medical Center, New York, NY 10032, USA
2
Graduate School of Arts and Sciences, Department of Pathobiology and Mechanisms of Disease, Columbia University Irving Medical Center, New York, NY 10032, USA
3
Department of Biological Sciences, Columbia University, New York, NY 10027, USA
4
Barnard College, Columbia University, New York, NY 10027, USA
5
Department of Pediatrics, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA
6
Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA
7
Eppley Institute for Research in Cancer and Allied Diseases, Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA
8
Division of Neuropathology, Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA
9
Department of Surgery, Columbia University Irving Medical Center, New York, NY 10032, USA
10
Department of Surgery, New York University Grossman School of Medicine, New York, NY 10016, USA
11
Department of Cell Biology, New York University Grossman School of Medicine, New York, NY 10016, USA
12
Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(1), 3; https://doi.org/10.3390/cancers12010003
Received: 4 November 2019 / Revised: 4 December 2019 / Accepted: 13 December 2019 / Published: 18 December 2019
(This article belongs to the Special Issue Cancer Cachexia)
Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer type in which the mortality rate approaches the incidence rate. More than 85% of PDAC patients experience a profound loss of muscle mass and function, known as cachexia. PDAC patients with this condition suffer from decreased tolerance to anti-cancer therapies and often succumb to premature death due to respiratory and cardiac muscle wasting. Yet, there are no approved therapies available to alleviate cachexia. We previously found that upregulation of the metal ion transporter, Zip14, and altered zinc homeostasis are critical mediators of cachexia in metastatic colon, lung, and breast cancer models. Here, we show that a similar mechanism is likely driving the development of cachexia in PDAC. In two independent experimental metastasis models generated from the murine PDAC cell lines, Pan02 and FC1242, we observed aberrant Zip14 expression and increased zinc ion levels in cachectic muscles. Moreover, in advanced PDAC patients, high levels of ZIP14 in muscles correlated with the presence of cachexia. These studies underscore the importance of altered ZIP14 function in PDAC-associated cachexia development and highlight a potential therapeutic opportunity for improving the quality of life and prolonging survival in PDAC patients. View Full-Text
Keywords: cachexia; ZIP14; Slc39a14; pancreatic cancer; pancreatic ductal adenocarcinoma; zinc transporter; zinc homeostasis; metastasis; muscle atrophy cachexia; ZIP14; Slc39a14; pancreatic cancer; pancreatic ductal adenocarcinoma; zinc transporter; zinc homeostasis; metastasis; muscle atrophy
Show Figures

Figure 1

MDPI and ACS Style

Shakri, A.R.; Zhong, T.J.; Ma, W.; Coker, C.; Kim, S.; Calluori, S.; Scholze, H.; Szabolcs, M.; Caffrey, T.; Grandgenett, P.M.; Hollingsworth, M.A.; Tanji, K.; Kluger, M.D.; Miller, G.; Biswas, A.K.; Acharyya, S. Upregulation of ZIP14 and Altered Zinc Homeostasis in Muscles in Pancreatic Cancer Cachexia. Cancers 2020, 12, 3.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop