Details

Autor(en) / Beteiligte

• Morita, Mami
• Sato, Taku
• Nomura, Miyuki
• Sakamoto, Yoshimi
• Inoue, Yui
• Tanaka, Ryota
• Ito, Shigemi
• Kurosawa, Koreyuki
• Yamaguchi, Kazunori
• Sugiura, Yuki
• Takizaki, Hiroshi
• Yamashita, Yoji
• Katakura, Ryuichi
• Sato, Ikuro
• Kawai, Masaaki
• Okada, Yoshinori
• Watanabe, Hitomi
• Kondoh, Gen
• Matsumoto, Shoko
• Kishimoto, Ayako
• Obata, Miki
• Matsumoto, Masaki
• Fukuhara, Tatsuro
• Motohashi, Hozumi
• Suematsu, Makoto
• Komatsu, Masaaki
• Nakayama, Keiichi I.
• Watanabe, Toshio
• Soga, Tomoyoshi
• Shima, Hiroshi
• Maemondo, Makoto
• Tanuma, Nobuhiro

Titel

PKM1 Confers Metabolic Advantages and Promotes Cell-Autonomous Tumor Cell Growth

Ist Teil von

• Cancer cell, 2018-03, Vol.33 (3), p.355-367.e7

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Expression of PKM2, which diverts glucose-derived carbon from catabolic to biosynthetic pathways, is a hallmark of cancer. However, PKM2 function in tumorigenesis remains controversial. Here, we show that, when expressed rather than PKM2, the PKM isoform PKM1 exhibits a tumor-promoting function in KRASG12D-induced or carcinogen-initiated mouse models or in some human cancers. Analysis of Pkm mutant mouse lines expressing specific PKM isoforms established that PKM1 boosts tumor growth cell intrinsically. PKM1 activated glucose catabolism and stimulated autophagy/mitophagy, favoring malignancy. Importantly, we observed that pulmonary neuroendocrine tumors (NETs), including small-cell lung cancer (SCLC), express PKM1, and that PKM1 expression is required for SCLC cell proliferation. Our findings provide a rationale for targeting PKM1 therapeutically in certain cancer subtypes, including pulmonary NETs. [Display omitted] •PKM1 promotes tumor growth cell intrinsically in some contexts•PKM1 activates glucose catabolism without interfering with biosynthetic pathways•PKM1-dependent autophagy/mitophagy contributes to malignancy•Expression of PKM1, but not PKM2, is sufficient to support SCLC cell proliferation The relative importance of PKM isoforms in tumor growth has been controversial. Morita et al. show that PKM1 promotes the growth of multiple tumor models using mouse lines expressing PKM1 or PKM2 from the endogenous Pkm locus. PKM1 is expressed in human SCLC, and it is important for SCLC cell proliferation.