Endocytosis: a Pivotal Pathway for Regulating Metastasis

Overview

Journal Br J Cancer

Specialty Oncology

Date 2020 Dec 2

PMID 33262521

Citations 62

Authors

Imran Khan

Patricia S Steeg

Affiliations

Soon will be listed here.

Abstract

A potentially important aspect in the regulation of tumour metastasis is endocytosis. This process consists of internalisation of cell-surface receptors via pinocytosis, phagocytosis or receptor-mediated endocytosis, the latter of which includes clathrin-, caveolae- and non-clathrin or caveolae-mediated mechanisms. Endocytosis then progresses through several intracellular compartments for sorting and routing of cargo, ending in lysosomal degradation, recycling back to the cell surface or secretion. Multiple endocytic proteins are dysregulated in cancer and regulate tumour metastasis, particularly migration and invasion. Importantly, four metastasis suppressor genes function in part by regulating endocytosis, namely, the NME, KAI, MTSS1 and KISS1 pathways. Data on metastasis suppressors identify a new point of dysregulation operative in tumour metastasis, alterations in signalling through endocytosis. This review will focus on the multicomponent process of endocytosis affecting different steps of metastasis and how metastatic-suppressor genes use endocytosis to suppress metastasis.

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References

Schmid S, Frolov V . Dynamin: functional design of a membrane fission catalyst. Annu Rev Cell Dev Biol. 2011; 27:79-105. DOI: 10.1146/annurev-cellbio-100109-104016. View

Hayer A, Stoeber M, Ritz D, Engel S, Meyer H, Helenius A . Caveolin-1 is ubiquitinated and targeted to intralumenal vesicles in endolysosomes for degradation. J Cell Biol. 2010; 191(3):615-29. PMC: 3003328. DOI: 10.1083/jcb.201003086. View

Rainero E, Howe J, Caswell P, Jamieson N, Anderson K, Critchley D . Ligand-Occupied Integrin Internalization Links Nutrient Signaling to Invasive Migration. Cell Rep. 2015; 10(3):398-413. DOI: 10.1016/j.celrep.2014.12.037. View

Novick P, Zerial M . The diversity of Rab proteins in vesicle transport. Curr Opin Cell Biol. 1997; 9(4):496-504. DOI: 10.1016/s0955-0674(97)80025-7. View

Dawson J, Timpson P, Kalna G, Machesky L . Mtss1 regulates epidermal growth factor signaling in head and neck squamous carcinoma cells. Oncogene. 2011; 31(14):1781-93. PMC: 3245856. DOI: 10.1038/onc.2011.376. View

L Kiss A . Caveolae and the regulation of endocytosis. Adv Exp Med Biol. 2012; 729:14-28. DOI: 10.1007/978-1-4614-1222-9_2. View

Xu B, Teng L, da Silva S, Bijian K, Al Bashir S, Jie S . The significance of dynamin 2 expression for prostate cancer progression, prognostication, and therapeutic targeting. Cancer Med. 2014; 3(1):14-24. PMC: 3930386. DOI: 10.1002/cam4.168. View

Parton R, Simons K . The multiple faces of caveolae. Nat Rev Mol Cell Biol. 2007; 8(3):185-94. DOI: 10.1038/nrm2122. View

Ignesti M, Barraco M, Nallamothu G, Woolworth J, Duchi S, Gargiulo G . Notch signaling during development requires the function of awd, the Drosophila homolog of human metastasis suppressor gene Nm23. BMC Biol. 2014; 12:12. PMC: 3937027. DOI: 10.1186/1741-7007-12-12. View

10.

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

11.

Ramsay A, Marshall J, Hart I . Integrin trafficking and its role in cancer metastasis. Cancer Metastasis Rev. 2007; 26(3-4):567-78. DOI: 10.1007/s10555-007-9078-7. View

12.

Kawana Y, Komiya A, Ueda T, Nihei N, Kuramochi H, Suzuki H . Location of KAI1 on the short arm of human chromosome 11 and frequency of allelic loss in advanced human prostate cancer. Prostate. 1997; 32(3):205-13. DOI: 10.1002/(sici)1097-0045(19970801)32:3<205::aid-pros7>3.0.co;2-j. View

13.

Cvetkovic D, Babwah A, Bhattacharya M . Kisspeptin/KISS1R System in Breast Cancer. J Cancer. 2013; 4(8):653-61. PMC: 3805993. DOI: 10.7150/jca.7626. View

14.

Boissan M, Montagnac G, Shen Q, Griparic L, Guitton J, Romao M . Membrane trafficking. Nucleoside diphosphate kinases fuel dynamin superfamily proteins with GTP for membrane remodeling. Science. 2014; 344(6191):1510-5. PMC: 4601533. DOI: 10.1126/science.1253768. View

15.

Christoforidis S, Miaczynska M, Ashman K, Wilm M, Zhao L, Yip S . Phosphatidylinositol-3-OH kinases are Rab5 effectors. Nat Cell Biol. 1999; 1(4):249-52. DOI: 10.1038/12075. View

16.

Ungewickell E, Ungewickell H, Holstein S, Lindner R, Prasad K, Barouch W . Role of auxilin in uncoating clathrin-coated vesicles. Nature. 1995; 378(6557):632-5. DOI: 10.1038/378632a0. View

17.

Mellman I, Yarden Y . Endocytosis and cancer. Cold Spring Harb Perspect Biol. 2013; 5(12):a016949. PMC: 3839607. DOI: 10.1101/cshperspect.a016949. View

18.

Donaldson J, Jackson C . ARF family G proteins and their regulators: roles in membrane transport, development and disease. Nat Rev Mol Cell Biol. 2011; 12(6):362-75. PMC: 3245550. DOI: 10.1038/nrm3117. View

19.

Malerod L, Stuffers S, Brech A, Stenmark H . Vps22/EAP30 in ESCRT-II mediates endosomal sorting of growth factor and chemokine receptors destined for lysosomal degradation. Traffic. 2007; 8(11):1617-29. DOI: 10.1111/j.1600-0854.2007.00630.x. View

20.

Alonso-Curbelo D, Riveiro-Falkenbach E, Perez-Guijarro E, Cifdaloz M, Karras P, Osterloh L . RAB7 controls melanoma progression by exploiting a lineage-specific wiring of the endolysosomal pathway. Cancer Cell. 2014; 26(1):61-76. DOI: 10.1016/j.ccr.2014.04.030. View