Disease-specific Alteration of Karyopherin-α Subtype Establishes Feed-forward Oncogenic Signaling in Head and Neck Squamous Cell Carcinoma

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2019 Dec 12

PMID 31822798

Citations 21

Authors

Masaharu Hazawa

Kie Sakai

Akiko Kobayashi

Hironori Yoshino

Yoshihiro Iga

Yuki Iwashima

Kee Sing Lim

Dominic Chih-Cheng Voon

Yan-Yi Jiang

Shin-Ichi Horike

De-Chen Lin

Richard W Wong

Affiliations

Soon will be listed here.

Abstract

Nuclear import, mediated in part by karyopherin-α (KPNA)/importin-α subtypes, regulates transcription factor access to the genome and determines cell fate. However, the cancer-specific changes of KPNA subtypes and the relevancy in cancer biology remain largely unknown. Here, we report that KPNA4, encoding karyopherin-α4 (KPNA4), is exclusively amplified and overexpressed in head and neck of squamous cell carcinoma (HNSCC). Depletion of KPNA4 attenuated nuclear localization signal-dependent transport activity and suppressed malignant phenotypes and induced epidermal differentiation. Mechanistically, KPNA4-mediated nuclear transport of Ras-responsive element-binding protein (RREB1), which sustains Ras/ERK pathway signaling through repressing miR-143/145 expression. Notably, MAPK signaling enhanced trafficking activity of KPNA4 via phosphorylation of KPNA4 at Ser60. These data reveal that KPNA4 establishes a feed-forward cascade that potentiates Ras/ERK signaling in HNSCC.

Citing Articles

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