Public RELEASE (Mar-13, ‘18)

Pkm1: potential new target for deadly lung cancer
MIYAGI CANCER CENTER RESEARCH INSTITUTE.

New report of how glucose is metabolized in small-cell lung cancer opens
avenues for molecular-targeted therapy
A team of Miyagi Cancer Center Research Institute(MCCRI) investigators in Japan has discovered a key
molecule regulating glucose metabolism in a subsetof lung cancers, namely small-cell lung cancer(SCLC). SCLC accounts for about 15% of lung cancers,
and patient prognosis in these cases is poorer thanthat of patients with other types of lung cancer.
Importantly, SCLC patients have not benefited fromrecent advances in cancer therapy as their tumors
display few druggable targets. The researchers haveshown that a glycolytic enzyme called Pkm1 confers
metabolic advantages to tumor cells and is required
for SCLC proliferation. Their findings are published in
the journal Cancer Cell on-line today.
Until now, Pkm1 has not been thought to be required for cancer cell proliferation. Using a genetic
approach in rodents, however, this study showed that Pkm1 promotes, rather than limits, cancer
cell proliferation. Pkm1 in fact activated glucose catabolism in tumor cells, enhancing malignancy.
Moreover, the group found that SCLC cells, one of the deadliest cancers known, specifically express
Pkm1 at high levels, unlike other cancer types. They also showed that active glucose metabolism
promoted by Pkm1 is required to sustain SCLC proliferation. These are unanticipated findings, since
many in the field previously thought that limiting glucose catabolism is a prerequisite fortumorigenesis.
“Our team has long observed that Pkm1 boosts, rather than inhibits, tumor cell growth in various
experimental models of SCLC,” says Nobu-hiro Tanuma, an oncologist and leader of the researchgroup. “Our new study explains this apparent discrepancy between our results and that of othersin the field by convincingly reporting that Pkm1 overall promotes, rather than inhibits, tumor cellproliferation in this type of lung cancer. These findings strongly suggest that Pkm1 and factors
related its activity are potential targets to treat SCLC.”
Support for the study includes JSPS grants, the Takeda Foundation, the Mochida Memorial
Foundation for Medical and Pharmaceutical Research, the Kato Memorial Bioscience Foundation,
the Uehara Memorial Foundation and the Sagawa Foundation for Promotion of Cancer Research###PUBLICATION DETAILS:TITLE: PKM1 confers metabolic advantages and promotes cell-autonomous tumor cell growth
AUTHORS: Morita M, Sato T, Nomura M, Sakamoto Y, Inoue Y, Tanaka R, Ito S, Kurosawa K, Yamaguchi
K, Sugiura Y, Takizaki H, Yamashita Y, Katakura R, Sato I, Okada Y, Watanabe H, Kondoh G,Matsumoto S, Kishimoto A, Obata M, Matsumoto M, Fukuhara T, Motohashi H, Suematsu
M, Komatsu M, Nakayama KI, Watanabe T, Soga T, Shima H, Maemondo M and Tanuma N
JOURNAL: Cancer Cell
DOI: 10.1016/j.ccell.2018.02.004
LINK: http://www.cell.com/cancer-cell/newarticles

CONTACT
Nobuhiro Tanuma, Division of Cancer Chemotherapy, Miyagi Cancer Center Research Institute,Japan. Email: ntanuma@med.tohoku.ac.jp

Pkm1: potential new target for deadly lung cancer (IMAGE)

CAPTION
New report of how glucose is metabolized in small-cell lung cancer opens avenues for moleculartargeted therapy.

CREDIT
Nobu-hiro Tanuma, Ph.D., MCCRI/Tohoku University

USAGE RESTRICTIONS
For educational use only