BAIAP2L1 enables cancer cell migration and facilitates phospho‐Cofilin asymmetry localization in the border cells

Abstract

Dear Editor,Cancer invasion and metastasis are among the most clinically relevant cancer hallmarks. Identification of molecular pathways that contribute to cancer cell motility a crucial step in cancer invasion/metastasis is essential to understanding how cancer motility is regulated and may provide therapeutic targets for treating metastatic cancer. Brain-specific angiogenesis inhibitor 1-associated protein 2-like protein 1 (BAIAP2L1) is a novel oncoprotein whose high-leveled expressions have been correlated with advanced and metastatic stages of cancer [1-3]. We have previously uncovered BAIAP2L1 as a novel oncogene by integrative analysis of protein-protein interactome and somatic copy number alterations in human cancers [4]. Although in vivo xenograft model showed that BAIAP2L1 promoted tumor growth [4], however, the exact mechanism by which BAIAP2L1 facilitates tumorigenesis remains unclear.We hypothesized that expressions of BAIAP2L1 were involved with metastatic/invasive phenotypes of cancer. To investigate, we selected the breast cancer cell line MCF7 which expressed an acceptable level of BAIAP2L1 mRNA (Supplementary Fig. S1). Detailed methods can be found in the Supplementary File. We depleted endogenous BAIAP2L1 in MCF7 by BAIAP2L1-specific shorthairpin RNAs (shRNAs) and measured cancer cell migration via wound-healing assay. We found that BAIAP2L1-

BAIAP2L1 accelerates breast cancer progression and chemoresistance by activating AKT signaling through binding with ribosomal protein L3

“…A recent study by Pipatpanyanugoon et al reported that BAIAP2L1 might promote cancer cell migration by modulating the phosphorylation of cofilin, 31 which was consistent with our finding that BAIAP2L1 might facilitate cancer cell motility; moreover, it has been proven that AKT signaling could dominate cofilin during cancer progression. 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 The AKT–cofilin axis is involved in chemotherapy resistance. 35 Further studies should explore whether cofilin is crucial in the AKT signaling pathway in promoting breast cancer progression.…”

“…[26][27][28][29][30] Our results revealed that BAIAP2L1 expression was increased in docetaxel-resistant cells and that BAIAP2L1 expression in breast cancer patients with poor chemotherapy responses, progression. [22][23][24][25][26][27][28][29][30][31][32][33][34] The AKT-cofilin axis is involved in chemotherapy resistance. 35 Further studies should explore whether cofilin is crucial in the AKT signaling pathway in promoting breast cancer progression.…”

Short peptides based on the conserved regions of MIEN1 protein exhibit anticancer activity by targeting the MIEN1 signaling pathway

“…This dual modulation inhibited src-driven proliferation, migration, and disrupted actin dynamics, impeding overall tumor dissemination ( 39 , 40 , 41 ). Nonphosphorylated cofilin is an activated form of cofilin and plays a crucial role in promoting actin polymerization and directional cell motility ( 42 ). The peptides also diminished NF-κB activity in DU-145 cells and reduced EGF-induced NF-κB nuclear translocation in MDA-MB-231 cells.…”