TY - JOUR TI - Localization of KRAS downstream target ARL4C to invasive pseudopods accelerates pancreatic cancer cell invasion AU - Harada, Akikazu AU - Matsumoto, Shinji AU - Yasumizu, Yoshiaki AU - Shojima, Kensaku AU - Akama, Toshiyuki AU - Eguchi, Hidetoshi AU - Kikuchi, Akira A2 - Postovit, Lynne-Marie A2 - Golemis, Erica A A2 - Nabi, Ivan Robert A2 - Leong, Hon VL - 10 PY - 2021 DA - 2021/09/30 SP - e66721 C1 - eLife 2021;10:e66721 DO - 10.7554/eLife.66721 UR - https://doi.org/10.7554/eLife.66721 AB - 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. KW - ARL4C KW - invasion KW - pancreatic cancer JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -