PINCH-1 regulates mitochondrial dynamics to promote proline synthesis and tumor growth

Ling Guo (), Chunhong Cui, Jiaxin Wang, Jifan Yuan, Qingyang Yang, Ping Zhang, Wen Su, Ruolu Bao, Jingchao Ran and Chuanyue Wu ()
Additional contact information
Ling Guo: Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Academy for Advanced Interdisciplinary Studies and Department of Biology, Southern University of Science and Technology
Chunhong Cui: Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Academy for Advanced Interdisciplinary Studies and Department of Biology, Southern University of Science and Technology
Jiaxin Wang: Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Academy for Advanced Interdisciplinary Studies and Department of Biology, Southern University of Science and Technology
Jifan Yuan: Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Academy for Advanced Interdisciplinary Studies and Department of Biology, Southern University of Science and Technology
Qingyang Yang: Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Academy for Advanced Interdisciplinary Studies and Department of Biology, Southern University of Science and Technology
Ping Zhang: Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Academy for Advanced Interdisciplinary Studies and Department of Biology, Southern University of Science and Technology
Wen Su: Shenzhen University Health Science Center
Ruolu Bao: Shenzhen University Health Science Center
Jingchao Ran: Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Academy for Advanced Interdisciplinary Studies and Department of Biology, Southern University of Science and Technology
Chuanyue Wu: University of Pittsburgh School of Medicine

Nature Communications, 2020, vol. 11, issue 1, 1-20

Abstract: Abstract Reprograming of proline metabolism is critical for tumor growth. Here we show that PINCH-1 is highly expressed in lung adenocarcinoma and promotes proline synthesis through regulation of mitochondrial dynamics. Knockout (KO) of PINCH-1 increases dynamin-related protein 1 (DRP1) expression and mitochondrial fragmentation, which suppresses kindlin-2 mitochondrial translocation and interaction with pyrroline-5-carboxylate reductase 1 (PYCR1), resulting in inhibition of proline synthesis and cell proliferation. Depletion of DRP1 reverses PINCH-1 deficiency-induced defects on mitochondrial dynamics, proline synthesis and cell proliferation. Furthermore, overexpression of PYCR1 in PINCH-1 KO cells restores proline synthesis and cell proliferation, and suppresses DRP1 expression and mitochondrial fragmentation. Finally, ablation of PINCH-1 from lung adenocarcinoma in mouse increases DRP1 expression and inhibits PYCR1 expression, proline synthesis, fibrosis and tumor growth. Our results identify a signaling axis consisting of PINCH-1, DRP1 and PYCR1 that regulates mitochondrial dynamics and proline synthesis, and suggest an attractive strategy for alleviation of tumor growth.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-020-18753-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18753-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-18753-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().