Endocytosis and Cancer

Overview

Journal Cold Spring Harb Perspect Biol

Specialties Biology
Molecular Biology

Date 2013 Dec 4

PMID 24296170

Citations 205

Authors

Ira Mellman

Yosef Yarden

Affiliations

Soon will be listed here.

Abstract

Endocytosis entails selective packaging of cell-surface proteins, such as receptors for cytokines and adhesion components, in cytoplasmic vesicles (endosomes). The series of sorting events that determines the fate of internalized proteins, either degradation in lysosomes or recycling back to the plasma membrane, relies on intrinsic sequence motifs, posttranslational modifications (e.g., phosphorylation and ubiquitination), and transient assemblies of both Rab GTPases and phosphoinositide-binding proteins. This multicomponent process is enhanced and skewed in cancer cells; we review mechanisms enabling both major drivers of cancer, p53 and Ras, to bias recycling of integrins and receptor tyrosine kinases (RTKs). Likewise, cadherins and other junctional proteins of cancer cells are constantly removed from the cell surface, thereby disrupting tissue polarity and instigating motile phenotypes. Mutant forms of RTKs able to evade Cbl-mediated ubiquitination, along with overexpression of the wild-type forms and a variety of defective feedback regulatory loops, are frequently detected in tumors. Finally, we describe pharmacological attempts to harness the peculiar endocytic system of cancer, in favor of effective patient treatment.

Citing Articles

Intestinal epithelial PTPN23 is essential for gut barrier integrity and prevention of fatal bacterial translocation.

Sanchez Alvarez R, Montalban-Arques A, Morsy Y, Gottier C, Hafliger J, Atrott K J Crohns Colitis. 2025; 19(2).

PMID: 39873381 PMC: 11815487. DOI: 10.1093/ecco-jcc/jjaf016.

Glucosylceramide Synthase Inhibition in Combination with Aripiprazole Sensitizes Hepatocellular Cancer Cells to Sorafenib and Doxorubicin.

Jennemann R, Volz M, Frias-Soler R, Schulze A, Richter K, Kaden S Int J Mol Sci. 2025; 26(1.

PMID: 39796160 PMC: 11720485. DOI: 10.3390/ijms26010304.

Non-coding RNAs in oral cancer: Emerging biomarkers and therapeutic frontier.

Hashemi M, Khoushab S, Hobabi Aghmiuni M, Anaraki S, Alimohammadi M, Taheriazam A Heliyon. 2024; 10(21):e40096.

PMID: 39583806 PMC: 11582460. DOI: 10.1016/j.heliyon.2024.e40096.

Sustained Endocytosis Inhibition via Locally-Injected Drug-Eluting Hydrogel Improves ADCC-Mediated Antibody Therapy in Colorectal Cancer.

Wu C, Liu X, Liu R, Song S, Zheng Z, Zeng Y Adv Sci (Weinh). 2024; 12(2):e2407239.

PMID: 39560161 PMC: 11727399. DOI: 10.1002/advs.202407239.

Clathrin-associated carriers enable recycling through a kiss-and-run mechanism.

Xu J, Liang Y, Li N, Dang S, Jiang A, Liu Y Nat Cell Biol. 2024; 26(10):1652-1668.

PMID: 39300312 DOI: 10.1038/s41556-024-01499-4.

References

Menju T, Hashimoto S, Hashimoto A, Otsuka Y, Handa H, Ogawa E . Engagement of overexpressed Her2 with GEP100 induces autonomous invasive activities and provides a biomarker for metastases of lung adenocarcinoma. PLoS One. 2011; 6(9):e25301. PMC: 3178645. DOI: 10.1371/journal.pone.0025301. View

Li J, Peters P, Bai M, Dai J, Bos E, Kirchhausen T . An ACAP1-containing clathrin coat complex for endocytic recycling. J Cell Biol. 2007; 178(3):453-64. PMC: 2064835. DOI: 10.1083/jcb.200608033. View

Pylayeva-Gupta Y, Grabocka E, Bar-Sagi D . RAS oncogenes: weaving a tumorigenic web. Nat Rev Cancer. 2011; 11(11):761-74. PMC: 3632399. DOI: 10.1038/nrc3106. View

Wong A, Bigner S, Bigner D, Kinzler K, Hamilton S, Vogelstein B . Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc Natl Acad Sci U S A. 1987; 84(19):6899-903. PMC: 299192. DOI: 10.1073/pnas.84.19.6899. View

Mellman I . Membranes and sorting. Curr Opin Cell Biol. 1996; 8(4):497-8. DOI: 10.1016/s0955-0674(96)80026-3. View

Anastasi S, Fiorentino L, Fiorini M, Fraioli R, Sala G, Castellani L . Feedback inhibition by RALT controls signal output by the ErbB network. Oncogene. 2003; 22(27):4221-34. DOI: 10.1038/sj.onc.1206516. View

Christoforides C, Rainero E, Brown K, Norman J, Toker A . PKD controls αvβ3 integrin recycling and tumor cell invasive migration through its substrate Rabaptin-5. Dev Cell. 2012; 23(3):560-72. PMC: 3443396. DOI: 10.1016/j.devcel.2012.08.008. View

Yin Y, Shen F, Pei H, Ding Y, Zhao H, Zhao M . Increased expression of Rab25 in breast cancer correlates with lymphatic metastasis. Tumour Biol. 2012; 33(5):1581-7. DOI: 10.1007/s13277-012-0412-5. View

Wang Y, Roche O, Yan M, Finak G, Evans A, Metcalf J . Regulation of endocytosis via the oxygen-sensing pathway. Nat Med. 2009; 15(3):319-24. DOI: 10.1038/nm.1922. View

10.

Ridge S, Worwood M, Oscier D, Jacobs A, Padua R . FMS mutations in myelodysplastic, leukemic, and normal subjects. Proc Natl Acad Sci U S A. 1990; 87(4):1377-80. PMC: 53478. DOI: 10.1073/pnas.87.4.1377. View

11.

Ezratty E, Partridge M, Gundersen G . Microtubule-induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase. Nat Cell Biol. 2005; 7(6):581-90. DOI: 10.1038/ncb1262. View

12.

Hynes N, MacDonald G . ErbB receptors and signaling pathways in cancer. Curr Opin Cell Biol. 2009; 21(2):177-84. DOI: 10.1016/j.ceb.2008.12.010. View

13.

Sigismund S, Argenzio E, Tosoni D, Cavallaro E, Polo S, Di Fiore P . Clathrin-mediated internalization is essential for sustained EGFR signaling but dispensable for degradation. Dev Cell. 2008; 15(2):209-19. DOI: 10.1016/j.devcel.2008.06.012. View

14.

Laplante M, Sabatini D . mTOR signaling in growth control and disease. Cell. 2012; 149(2):274-93. PMC: 3331679. DOI: 10.1016/j.cell.2012.03.017. View

15.

Lu A, Tebar F, Alvarez-Moya B, Lopez-Alcala C, Calvo M, Enrich C . A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes. J Cell Biol. 2009; 184(6):863-79. PMC: 2699148. DOI: 10.1083/jcb.200807186. View

16.

Caswell P, Spence H, Parsons M, White D, Clark K, Cheng K . Rab25 associates with alpha5beta1 integrin to promote invasive migration in 3D microenvironments. Dev Cell. 2007; 13(4):496-510. DOI: 10.1016/j.devcel.2007.08.012. View

17.

van der Horst E, Degenhardt Y, Strelow A, Slavin A, Chinn L, Orf J . Metastatic properties and genomic amplification of the tyrosine kinase gene ACK1. Proc Natl Acad Sci U S A. 2005; 102(44):15901-6. PMC: 1276100. DOI: 10.1073/pnas.0508014102. View

18.

Bridge J, Kanamori M, Ma Z, Pickering D, Hill D, Lydiatt W . Fusion of the ALK gene to the clathrin heavy chain gene, CLTC, in inflammatory myofibroblastic tumor. Am J Pathol. 2001; 159(2):411-5. PMC: 1850566. DOI: 10.1016/S0002-9440(10)61711-7. View

19.

Katzmann D, Babst M, Emr S . Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell. 2001; 106(2):145-55. DOI: 10.1016/s0092-8674(01)00434-2. View

20.

Ruan D, Warren R, Moalem J, Chung K, Griffin A, Shen W . Mitogen-inducible gene-6 expression correlates with survival and is an independent predictor of recurrence in BRAF(V600E) positive papillary thyroid cancers. Surgery. 2008; 144(6):908-13. DOI: 10.1016/j.surg.2008.07.028. View