AKR1B10 negatively regulates autophagy through reducing GAPDH upon glucose starvation in colon cancer

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ABSTRACT

Autophagy is considered to be an important switch for facilitating normal to malignant cell transformation during colorectal cancer development. Consistent with other reports, we found that the membrane receptor Neuropilin1 (NRP1) is greatly upregulated in colon cancer cells that underwent autophagy upon glucose deprivation. However, the mechanism underlying NRP1 regulation of autophagy is unknown. We found that knockdown of NRP1 inhibits autophagy and largely upregulates the expression of aldo-keto reductase family 1 B10 (AKR1B10). Moreover, we demonstrated that AKR1B10 interacts with and inhibits the nuclear importation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and then subsequently represses autophagy. Interestingly, we also found that an NADPH-dependent reduction reaction could be induced when AKR1B10 interacts with GAPDH, and the reductase activity of AKR1B10 is important for its repression of autophagy. Together, our findings unravel a novel mechanism of NRP1 in regulating autophagy through AKR1B10.

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Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)

This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.

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AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1.

Joungmok Kim, Mondira Kundu, Benoit Viollet … (2011)

Autophagy is a process by which components of the cell are degraded to maintain essential activity and viability in response to nutrient limitation. Extensive genetic studies have shown that the yeast ATG1 kinase has an essential role in autophagy induction. Furthermore, autophagy is promoted by AMP activated protein kinase (AMPK), which is a key energy sensor and regulates cellular metabolism to maintain energy homeostasis. Conversely, autophagy is inhibited by the mammalian target of rapamycin (mTOR), a central cell-growth regulator that integrates growth factor and nutrient signals. Here we demonstrate a molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1. Under glucose starvation, AMPK promotes autophagy by directly activating Ulk1 through phosphorylation of Ser 317 and Ser 777. Under nutrient sufficiency, high mTOR activity prevents Ulk1 activation by phosphorylating Ulk1 Ser 757 and disrupting the interaction between Ulk1 and AMPK. This coordinated phosphorylation is important for Ulk1 in autophagy induction. Our study has revealed a signalling mechanism for Ulk1 regulation and autophagy induction in response to nutrient signalling.

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Cancer statistics, 2014.

Rebecca Siegel, Jiemin Ma, Zhaohui Zou … (2014)

Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths that will occur in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival. Incidence data were collected by the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data were collected by the National Center for Health Statistics. A total of 1,665,540 new cancer cases and 585,720 cancer deaths are projected to occur in the United States in 2014. During the most recent 5 years for which there are data (2006-2010), delay-adjusted cancer incidence rates declined slightly in men (by 0.6% per year) and were stable in women, while cancer death rates decreased by 1.8% per year in men and by 1.4% per year in women. The combined cancer death rate (deaths per 100,000 population) has been continuously declining for 2 decades, from a peak of 215.1 in 1991 to 171.8 in 2010. This 20% decline translates to the avoidance of approximately 1,340,400 cancer deaths (952,700 among men and 387,700 among women) during this time period. The magnitude of the decline in cancer death rates from 1991 to 2010 varies substantially by age, race, and sex, ranging from no decline among white women aged 80 years and older to a 55% decline among black men aged 40 years to 49 years. Notably, black men experienced the largest drop within every 10-year age group. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population. © 2014 American Cancer Society, Inc.

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Author and article information

Contributors

Wanyun Li: (View ORCID Profile)

Cong Liu: (View ORCID Profile)

Zilan Huang: (View ORCID Profile)

Lei Shi: (View ORCID Profile)

Wenwen Zhou: (View ORCID Profile)

Peipei Meng: (View ORCID Profile)

Fanghong Luo: (View ORCID Profile)

Jianghua Yan: (View ORCID Profile)

Ting Wu: (View ORCID Profile)

Journal

Title: Journal of Cell Science

Publisher: The Company of Biologists

ISSN (Print): 0021-9533

ISSN (Electronic): 1477-9137

Publication date Created: April 15 2021

Publication date (Print): April 15 2021

Publication date (Electronic): April 22 2021

Volume: 134

Issue: 8

Affiliations

[1 ]Cancer Research Center, School of Medicine, Xiamen University, Xiamen 361000, China

[2 ]State Key Laboratory of Cellular Stress Biology, Innovation Center for Cellular Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361000, China

[3 ]Department of Basic Medicine, School of Medicine, Xiamen University, Xiamen 361000, China

[4 ]Xiamen University Research Center of Retroperitoneal Tumor Committee of Oncology Society of Chinese Medical Association, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361000, China

[5 ]Joint Laboratory of Xiamen University School of Medicine and Shanghai Jiangxia Blood Technology Co., Ltd., Xiamen 361000, China

Article

DOI: 10.1242/jcs.255273

PubMed ID: 33758077

SO-VID: 5bef75aa-0af4-4aee-9ef8-0ae7f5497c77

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http://www.biologists.com/user-licence-1-1/

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