TARGETS

 

Master Invadopodial Regulator 1 (MIR-01)

MIR-01 is a master regulator of invadopodia and cancer invasiveness, playing a dominant role similar to oncogenic RAS in cancer formation. Antapodia Therapeutics pioneered the identification of MIR-01 as a critical component of a protein complex that initiates invadopodia formation. Aside from its role in invadopodia, MIR-01 also serves as a positive regulator of developmental pathways (Wnt, Notch, Hedgehog, FoxM1) and stem-cell gene expression (OCT4, SOX2, KLF4, EZH2, MYC), thereby promoting tumor growth and progression (Figure 1). In invasive cancer cells, MIR-01 predominantly localizes to the invadopodia (Figure 2). Notably and importantly, MIR-01 is encoded by a transcript variant whose expression is specifically upregulated in cancer cells, making it an ideal and safe therapeutic target (Figure 3). Our mechanisms of action studies show that MIR-01 is indispensable for the formation of invadopodia in invasive cancer cells (Figure 4), thereby inhibiting cancer invasiveness (Figure 5) and distant metastasis in various types of cancers (Figure 6). In keeping with the pleiotropic roles of MIR-01, knockdown of its expression also substantially reduces the activities of Wnt, Notch, and Hedgehog pathway activities as well as the expression levels of multiple stemness genes in cancer cells (Figure 7).

Figure 1. MIR-01 mediates cancer metastasis and growth by regulating invadopodia and developmental pathways

Figure 1. MIR-1 is specifically localized to the invadopodia in invasive cancer cells

Figure 2. MIR-01 is specifically localized to the invadopodia on invasive cancer cells

Figure 1. MIR-1 is specifically localized to the invadopodia in invasive cancer cells

Figure 3. MIR-01 expression is upregulated in the cytoplasm of HCC (A) and TNBC cells (B)

Figure 2. MIR-1 expression is upregulated in cancer cells

HCC, hepatocellular carcinoma; TNBC, triple-negative breast cancer.

Figure 4. Genetic knockdown of MIR-01 abrogates the invadopodial formation in invasive cancer cells

Figure 3. Genetic knockdown of MIR-1 abrogates invadopodia formation in invasive cancer cells

Invadopodia are represented by cortactin and F-actin colocalized dots (yellow) in these confocal images.

Figure 5. Genetic knockdown of MIR-01 markedly attenuates the invasiveness of cancer cells

Figure 4. Genetic knockdown of MIR-1 abrogates cancer cell invasiveness

Figure 6. Genetic knockdown of MIR-01 abolishes cancer metastasis

Figure 5. Genetic knockdown of MIR-1 cancels cancer metastasis

TNBC, triple-negative breast cancer; NSCLC, non-small cell lung cancer; PDAC, pancreatic ductal epithelial cancer

Figure 7. Genetic knockdown of MIR-01 inhibits develpmental pathway activites and stemness gene expression in cancer cells

Figure 5. Genetic knockdown of MIR-1 cancels cancer metastasis

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Designed by Justin V. Tsai in 2021

Copyright © Antapodia Therapeutics, Inc., WA, USA. All Rights Reserved.

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