The high quality of the field in Dubai forced Pennetta, No. 22 in the rankings, to go through the qualifying round to reach the main draw. She's made the most of the chance, with a first-round win over Kaia Kanepi and then taking out Radwanska 6-4, 6-1 in the second round.
Radwanska jumped out to a 4-1 lead but Pennetta turned the match around by winning the next eight games.
Carla Suarez Navarro and Sorana Cirstea also ousted high seeds. Suarez Navarro completed the second round with a 1-6, 6-4, 7-6 (7-4) decision over third-seeded Petra Kvitova with a pair of breaks in each of the second and third sets. Cirstea defeated No. 4 Sara Errani 6-2, 5-7, 6-1. Cirstea claimed nearly 60 percent of the points in the third set and seven breaks in Errani's 13 games serving.
No. 5-seeded Jelena Jankovic earned a quarterfinal slot opposite world No. 1 Serena Williams with a 7-5, 6-4 decision over Lucie Safarova and eighth-seeded Caroline Wozniacki piled up eight breaks in a 6-4, 6-4 win over Annika Beck.
Venus Williams raced through a 6-3, 6-1 rout of Ana Ivanovic. Williams was good on just 43 percent of her first serves but still won three-quarters of the points on serve and saved both break points she faced in a 56-minute match.
Also in the second round Wednesday, Alize Cornet defeated Kirsten Flipkens 6-3, 6-4.