Localization of KRAS downstream target ARL4C to invasive pseudopods accelerates pancreatic cancer cell invasion

Pancreatic cancer has a high mortality rate due to metastasis. Whereas KRAS is mutated in most pancreatic cancer patients, controlling KRAS or its downstream effectors has not been succeeded clinically. ARL4C is a small G protein whose expression is induced by the Wnt and EGF–RAS pathways. In the pr...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Akikazu Harada, Shinji Matsumoto, Yoshiaki Yasumizu, Kensaku Shojima, Toshiyuki Akama, Hidetoshi Eguchi, Akira Kikuchi
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	ARL4C invasion pancreatic cancer Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5fbe9fa95757439f8c5ea656d83a9bfd
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5fbe9fa95757439f8c5ea656d83a9bfd
record_format	dspace
spelling	oai:doaj.org-article:5fbe9fa95757439f8c5ea656d83a9bfd2021-11-17T09:54:14ZLocalization of KRAS downstream target ARL4C to invasive pseudopods accelerates pancreatic cancer cell invasion10.7554/eLife.667212050-084Xe66721https://doaj.org/article/5fbe9fa95757439f8c5ea656d83a9bfd2021-09-01T00:00:00Zhttps://elifesciences.org/articles/66721https://doaj.org/toc/2050-084XPancreatic cancer has a high mortality rate due to metastasis. Whereas KRAS is mutated in most pancreatic cancer patients, controlling KRAS or its downstream effectors has not been succeeded clinically. ARL4C is a small G protein whose expression is induced by the Wnt and EGF–RAS pathways. In the present study, we found that ARL4C is frequently overexpressed in pancreatic cancer patients and showed that its localization to invasive pseudopods is required for cancer cell invasion. IQGAP1 was identified as a novel interacting protein for ARL4C. ARL4C recruited IQGAP1 and its downstream effector, MMP14, to invasive pseudopods. Specific localization of ARL4C, IQGAP1, and MMP14 was the active site of invasion, which induced degradation of the extracellular matrix. Moreover, subcutaneously injected antisense oligonucleotide against ARL4C into tumor-bearing mice suppressed metastasis of pancreatic cancer. These results suggest that ARL4C–IQGAP1–MMP14 signaling is activated at invasive pseudopods of pancreatic cancer cells.Akikazu HaradaShinji MatsumotoYoshiaki YasumizuKensaku ShojimaToshiyuki AkamaHidetoshi EguchiAkira KikuchieLife Sciences Publications LtdarticleARL4Cinvasionpancreatic cancerMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ARL4C invasion pancreatic cancer Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	ARL4C invasion pancreatic cancer Medicine R Science Q Biology (General) QH301-705.5 Akikazu Harada Shinji Matsumoto Yoshiaki Yasumizu Kensaku Shojima Toshiyuki Akama Hidetoshi Eguchi Akira Kikuchi Localization of KRAS downstream target ARL4C to invasive pseudopods accelerates pancreatic cancer cell invasion
description	Pancreatic cancer has a high mortality rate due to metastasis. Whereas KRAS is mutated in most pancreatic cancer patients, controlling KRAS or its downstream effectors has not been succeeded clinically. ARL4C is a small G protein whose expression is induced by the Wnt and EGF–RAS pathways. In the present study, we found that ARL4C is frequently overexpressed in pancreatic cancer patients and showed that its localization to invasive pseudopods is required for cancer cell invasion. IQGAP1 was identified as a novel interacting protein for ARL4C. ARL4C recruited IQGAP1 and its downstream effector, MMP14, to invasive pseudopods. Specific localization of ARL4C, IQGAP1, and MMP14 was the active site of invasion, which induced degradation of the extracellular matrix. Moreover, subcutaneously injected antisense oligonucleotide against ARL4C into tumor-bearing mice suppressed metastasis of pancreatic cancer. These results suggest that ARL4C–IQGAP1–MMP14 signaling is activated at invasive pseudopods of pancreatic cancer cells.
format	article
author	Akikazu Harada Shinji Matsumoto Yoshiaki Yasumizu Kensaku Shojima Toshiyuki Akama Hidetoshi Eguchi Akira Kikuchi
author_facet	Akikazu Harada Shinji Matsumoto Yoshiaki Yasumizu Kensaku Shojima Toshiyuki Akama Hidetoshi Eguchi Akira Kikuchi
author_sort	Akikazu Harada
title	Localization of KRAS downstream target ARL4C to invasive pseudopods accelerates pancreatic cancer cell invasion
title_short	Localization of KRAS downstream target ARL4C to invasive pseudopods accelerates pancreatic cancer cell invasion
title_full	Localization of KRAS downstream target ARL4C to invasive pseudopods accelerates pancreatic cancer cell invasion
title_fullStr	Localization of KRAS downstream target ARL4C to invasive pseudopods accelerates pancreatic cancer cell invasion
title_full_unstemmed	Localization of KRAS downstream target ARL4C to invasive pseudopods accelerates pancreatic cancer cell invasion
title_sort	localization of kras downstream target arl4c to invasive pseudopods accelerates pancreatic cancer cell invasion
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/5fbe9fa95757439f8c5ea656d83a9bfd
work_keys_str_mv	AT akikazuharada localizationofkrasdownstreamtargetarl4ctoinvasivepseudopodsacceleratespancreaticcancercellinvasion AT shinjimatsumoto localizationofkrasdownstreamtargetarl4ctoinvasivepseudopodsacceleratespancreaticcancercellinvasion AT yoshiakiyasumizu localizationofkrasdownstreamtargetarl4ctoinvasivepseudopodsacceleratespancreaticcancercellinvasion AT kensakushojima localizationofkrasdownstreamtargetarl4ctoinvasivepseudopodsacceleratespancreaticcancercellinvasion AT toshiyukiakama localizationofkrasdownstreamtargetarl4ctoinvasivepseudopodsacceleratespancreaticcancercellinvasion AT hidetoshieguchi localizationofkrasdownstreamtargetarl4ctoinvasivepseudopodsacceleratespancreaticcancercellinvasion AT akirakikuchi localizationofkrasdownstreamtargetarl4ctoinvasivepseudopodsacceleratespancreaticcancercellinvasion
_version_	1718425612948865024

Localization of KRAS downstream target ARL4C to invasive pseudopods accelerates pancreatic cancer cell invasion

Ejemplares similares