TARGETS

 

Master Invadopodial Regulator 1 (MIR-01)

MIR-01 is the master regulator of invadopodia biogenesis in invasive cancer cells, which plays a dominant role similar to the "KRAS" gene in the tumorigenesis of some human cancers. The scientists at Antapodia Biotherapeutics pioneered the identification of MIR-01 as a critical component of a novel planar cell polarity protein complex that functions to initiate invadopodia biogenesis. On the other hand, MIR-01 is also a critical coregulator of Wnt signaling and cell proliferation in cancer cells. MIR-01 is predominantly localized to the submembranous region of the invadopodia on invasive cancer cells across different types of human cancers (Figure 1). The expression of MIR-01 is specifically upregulated in cancer cells compared with normal epithelial cells, making it an ideal and safe therapeutic target (Figure 2). Genetic knockdown of MIR-01 blocks the formation of invadopodia in invasive cancer cells (Figure 3), thereby inhibiting cancer invasiveness (Figure 4) and distant metastasis (Figure 5) in various types of invasive cancers, including pancreatic, breast, lung, and prostate cancers.

Figure 1. 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 2. MIR-01 expression is specifically upregulated in the cytoplasm of TNBC tissues (A) and PDAC cells (B).

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

TNBC, triple-negative breast cancer; PDAC, pancreatic ductal epithelial cancer; BxPC-3, MIA Paca-2, and PANC-1 are all PDAC cell lines.

Figure 3. 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 4. Genetic knockdown of MIR-01 markedly attenuates the invasiveness of cancer cells

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

Figure 5. 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

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